Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

BACKGROUND: Emergence of the coronavirus disease (COVID-19) caught the world off guard and unprepared, initiating a global pandemic. In the absence of evidence, individual communities had to take timely action to reduce the rate of disease spread and avoid overburdening their health care systems. Although a few predictive models have been published to guide these decisions, most have not taken into account spatial differences and have included assumptions that do not match the local realities. Access to reliable information that is adapted to local context is critical for policy makers to make informed decisions during a rapidly evolving pandemic. OBJECTIVE: The goal of this study was to develop an adapted susceptible-infected-removed (SIR) model to predict the trajectory of the COVID-19 pandemic in North Carolina and the Charlotte Metropolitan Region, and to incorporate the effect of a public health intervention to reduce disease spread while accounting for unique regional features and imperfect detection. METHODS: Three SIR models were fit to infection prevalence data from North Carolina and the greater Charlotte Region and then rigorously compared. One of these models (SIR-int) accounted for a stay-at-home intervention and imperfect detection of COVID-19 cases. We computed longitudinal total estimates of the susceptible, infected, and removed compartments of both populations, along with other pandemic characteristics such as the basic reproduction number. RESULTS: Prior to March 26, disease spread was rapid at the pandemic onset with the Charlotte Region doubling time of 2.56 days (95% CI 2.11-3.25) and in North Carolina 2.94 days (95% CI 2.33-4.00). Subsequently, disease spread significantly slowed with doubling times increased in the Charlotte Region to 4.70 days (95% CI 3.77-6.22) and in North Carolina to 4.01 days (95% CI 3.43-4.83). Reflecting spatial differences, this deceleration favored the greater Charlotte Region compared to North Carolina as a whole. A comparison of the efficacy of intervention, defined as 1 - the hazard ratio of infection, gave 0.25 for North Carolina and 0.43 for the Charlotte Region. In addition, early in the pandemic, the initial basic SIR model had good fit to the data; however, as the pandemic and local conditions evolved, the SIR-int model emerged as the model with better fit. CONCLUSIONS: Using local data and continuous attention to model adaptation, our findings have enabled policy makers, public health officials, and health systems to proactively plan capacity and evaluate the impact of a public health intervention. Our SIR-int model for estimated latent prevalence was reasonably flexible, highly accurate, and demonstrated efficacy of a stay-at-home order at both the state and regional level. Our results highlight the importance of incorporating local context into pandemic forecast modeling, as well as the need to remain vigilant and informed by the data as we enter into a critical period of the outbreak.

Four decades of neoliberal health policies have left the United States with a health care system that prioritizes the profits of large corporate actors, denies needed care to tens of millions, is extraordinarily fragmented and inefficient, and was ill prepared to address the COVID-19 pandemic. The payment system has long rewarded hospitals for providing elective surgical procedures to well-insured patients while penalizing those providing the most essential and urgent services, causing hospital revenues to plummet as elective procedures were cancelled during the pandemic. Before the recession caused by the pandemic, tens of millions of Americans were unable to afford care, compromising their physical and financial health; deep-pocketed corporate interests were increasingly dominating the hospital industry and taking over physicians' practices; and insurers' profits hit record levels. Meanwhile, yawning class-based and racial inequities in care and health outcomes remain and have even widened. Recent data highlight the failure of policy strategies based on market models and the need to shift to a nonprofit social insurance model.

The global SARS-CoV-2 pandemic started late 2019 and currently continues unabated. The lag-time for developing vaccines means it is of paramount importance to be able to quickly develop and repurpose therapeutic drugs. Protein-based biosensors allow screening to be performed using routine molecular laboratory equipment without a need for expensive chemical reagents. Here we present a biosensor for the 3-chymotrypsin-like cysteine protease from SARS-CoV-2, comprising a FRET-capable pair of fluorescent proteins held in proximity by a protease cleavable linker. We demonstrate the utility of this biosensor for inhibitor discovery by screening 1280 compounds from the Library of Pharmaceutically Active Compounds collection. The screening identified 65 inhibitors, with the 20 most active exhibiting sub-micromolar inhibition of 3CL(pro) in follow-up EC50 assays. The top hits included several compounds not previously identified as 3CL(pro) inhibitors, in particular five members of a family of aporphine alkaloids that offer promise as new antiviral drug leads.

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

Rational: In March 2020, the World Health Organization (WHO) declared the coronavirus infectious disease as a pandemic referred to as COVID-19. As an essential service, community pharmacists have been enacting a key role in patient counseling and supply of essential medicines and protective equipment. Objectives: To investigate pharmacists' perspectives of the role of educational institutes and professional pharmacy organizations in supporting them to take on roles during COVID-19 pandemic and to identify barriers to be able to support themselves and their patients. Methods: This descriptive mixed-method study was conducted via a cross-sectional online survey distributed to pharmacists/pharmacy students in Jordan during the COVID-19 outbreak (15-30 March 2020) using an online questionnaire, followed by an online focus group. Questionnaire items related to participants' perspectives in being prepared for and supported in their roles during the COVID-19 pandemic, and items were tested for face validity. Data were descriptively analyzed using the Statistical Package for the Social Sciences and triangulated with focus group findings. Results: Considering that fear and anxiety are a consequence of mass social distancing/quarantine, study participants (n = 726, age = 26.9 (SD = 8.0) years, 71.9% females), reported needing training on mental healthcare to be able to support themselves and people during pandemics (90.2%). Most respondents agreed/strongly agreed (59.7%) with the statement around pharmacy educators/educational institutes having a key role in preparing pharmacists for practice during epidemics/pandemics and agreed that their faculties should add a course regarding pandemic preparedness in their curriculum (89.9%). Results were similar regarding roles for the pharmaceutical associations. Focus group findings (n = 7) mirrored the survey findings to a large extent. Conclusions: Most participants believed that pharmacy educators and pharmaceutical associations have a role in preparing them to deal with the COVID-19 pandemic through online educational workshops/webinars. Online education on mental healthcare is specifically needed.

PURPOSE: Cryoablation is a minimally-invasive percutaneous procedure that is capable of reducing the psychosocial burden of surgical delay while also decreasing the morbidity of breast cancer therapy. The purpose of this editorial is to discuss the potential role of cryoablation for reducing the psychosocial burden of surgical delay during the COVID-19 pandemic by expediting the management of breast cancer while also lessening demand on limited healthcare resources. METHODS: This editorial critiques current expert opinion recommendations that aim to reduce viral transmission and preserve healthcare resources during the COVID-19 pandemic by advocating delay of elective breast cancer surgery. RESULTS: The editorial summarizes the current state of the evidence that supports the selective use of cryoablation as a definite or stopgap measure in the management of breast cancer during the COVID-19 pandemic or when healthcare resources are limited. CONCLUSIONS: As an office-based procedure performed under local anesthesia, cryoablation eliminates the need for operating room personnel and equipment while also reducing the psychosocial impact of delayed breast cancer surgery. By reducing the number of patient and healthcare provider interactions, cryoablation not only decreases the risk of viral transmission but also the need for personal protective devices during resource-limited times.

Background: From March to May 2020, lockdown measures were adopted in Italy to contain the epidemic of the novel Coronavirus. People were forced to restrict their movement and social contacts, therefore having a higher risk of inactivity. This study, carried out among Italian undergraduates, explored their sedentary and physical activities (PA) during the lockdown with respect to their previous habits. Methods: An electronic questionnaire was administered once to students attending three Italian universities after the end of lockdown. Results: A total of 1430 students (mean age 22.9 +/- 3.5 years, 65.5% females) completed the questionnaire. All the sedentary behaviors increased significantly, and all the physical activities decreased significantly during the lockdown. Time spent using electronic devices showed the highest increase (+52.4 min/day), and walking the greatest decrease (-365.5 min/week). Being younger than 22 years old, female, and previously active, attending the universities of Naples and Rome and having at least one graduate parent were associated with the achievement of recommended levels of PA even during the lockdown. Conclusions: This study highlights the reduction of PA among Italian undergraduates in the course of home-confinement due to the CoViD-19 pandemic. The practice of adequate PA during the lockdown was mainly associated with the previous adoption of an active lifestyle. Promoting active lifestyles during the non-pandemic period may have had positive effects also in case of lockdown.

The experiences of these recent months have left us with as many new questions as they have given us new solutions. The main question that infection prevention and control department is having these days is "Why have hospital-associated infections (HAIs) reduced during COVID-19 pandemic?" What is the one unique strategy that has brought decline in increasing HAIs? Would it be appropriate to say that rigorous hand hygiene practices among health care workers (HCWs) have reduced HAIs in a tertiary care hospital of Pakistan? This commentary is written to understand the effect of rigorous hand hygiene among HCWs on number of HAIs during COVID-19 pandemic. Given the seriousness of this outbreak, it was observed that the hand hygiene has occupied a new place of importance in the minds of HCWs. We observed 4 times increase in the consumption of hand sanitizers after COVID-19 outbreak. The increased consumption of hand sanitizers was reflected in improved hand hygiene practices. A reduction was observed in the number of HAIs after the COVID-19 outbreak, and we assume that the dip in HAIs is associated with the improvement in hand hygiene practices in the recent months. In the wake of COVID-19 pandemic, these trends reassure us that hand hygiene compliance by HCWs alone can be effective in reducing HAIs in a hospital setting.

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.

BACKGROUND: Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated. METHODS: We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20). RESULTS: Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS). CONCLUSIONS: Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.

Since coronavirus disease 2019 (COVID-19) might circulate in the following seasons, it is essential to understand how COVID-19 influences other respiratory diseases, especially influenza. In this study, we analyzed the influenza activity from mid-November 2019 to March 2020 in Chinese mainland and found that the influenza season ended much earlier than previous seasons for all subtypes and lineages, which may have resulted from the circulation of COVID-19 and measures such as travel control and personal protection. These findings provide rudimentary knowledge of the co-circulation patterns of the two types of viruses.

The purpose of this study was to examine the deltoid skin biopsy in twenty-three patients with coronavirus disease 2019 (COVID-19), most severely ill, for vascular complement deposition and correlate this with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA and protein localization and ACE2 expression. Deltoid skin microvascular complement screening has been applied to patients with various systemic complement-mediated microvascular syndromes, best exemplified by atypical hemolytic uremic syndrome. In 21 of 23 cases, substantial microvascular deposition of complement components was identified. The two patients without significant complement deposition included one patient with moderate disease and a severely ill patient who although on a ventilator for a day was discharged after 3 days. The dominant microvascular complement immunoreactant identified was the terminal membranolytic attack complex C5b-9. Microvascular complement deposition strongly colocalized in situ with the SARS-CoV-2 viral proteins including spike glycoproteins in the endothelial cells as well as the viral receptor ACE2 in lesional and nonlesional skin; viral RNA was not evident. Microvascular SARS-CoV-2 viral protein, complement, and ACE2 expression was most conspicuous in the subcutaneous fat. Although the samples from severely ill patients with COVID-19 were from grossly normal skin, light microscopically focal microvascular abnormalities were evident that included endothelial cell denudement, basement membrane zone reduplication, and small thrombi. It is concluded that complement activation is common in grossly normal skin, especially in the subcutaneous fat which may provide a link between severe disease and obesity, in people with severe COVID-19, and the strong colocalization with the ACE2 receptor and viral capsid proteins without viral RNA suggests that circulating viral proteins (ie, pseudovirions) may dock onto the endothelial of these microvessels and induce complement activation.

The Covid-19 pandemic has markedly changed our practices. This article analyses the risks of contamination among healthcare professionals (HCPs) during laparoscopic surgery on patients with Covid-19. Harmful effects of aerosols from a pneumoperitoneum, with the virus present, have not yet been quantified. Measures for the protection of HCPs are an extrapolation of those taken during other epidemics. They must still be mandatory to minimise the risk of viral contamination. Protection measures include personal protection equipment for HCPs, adaptation of surgical technique (method for obtaining pneumoperitoneum, filters, preferred intracorporeal anastomosis, precautions during the exsufflation of the pneumoperitoneum), and organisation of the operating room.

Introduction: The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed since December 2019. It has caused a global pandemic with more than three hundred thousand case fatalities. However, apart from supportive care by respirators, no standard medical therapy is validated. Areas covered: This paper presents old drugs with potential in vitro efficacy against SARS-CoV-2. The in vitro database, adverse effects, and potential toxicities of these drugs are reviewed regarding their feasibility of clinical prescription for the treatment of patients with COVID-19. To obtain convincing recommendations, we referred to opinions from the US National Institute of Health regarding drugs repurposed for COVID-19 therapy. Expert opinion: Although strong evidence of well-designed randomized controlled studies regarding COVID-19 therapy is presently lacking, remdesivir, teicoplanin, hydroxychloroquine (not in combination with azithromycin), and ivermectin might be effective antiviral drugs and are deemed promising candidates for controlling SARS-CoV-2. In addition, tocilizumab might be considered as the supplementary treatment for COVID-19 patients with cytokine release syndrome. In future, clinical trials regarding a combination of potentially effective drugs against SARS-CoV-2 need to be conducted to establish the optimal regimen for the treatment of patients with moderate-to-severe COVID-19.

SARS-CoV-2, a newly emerged pathogen in December 2019, marked as one of the highly pathogenic Coronavirus, and altogether this is the third coronavirus attack that crossed the species barrier. As of 1(st) July 2020, it is spreading around 216 countries, areas or territories, and a total of 10,185,374 and 503,862 confirmed cases and death reports, respectively. The SARS-CoV-2 virus entered into the target cells by binding with the hACE2 receptors. Spike glycoprotein promotes the entry of the virus into host target cells. Literature reported a significant mutation in receptor binding sites and membrane proteins of the previous SARS-CoV to turned as SARS-CoV-2 virus, responsible for most dreadful pandemic COVID-19. These modifications may be the probable reason for the extreme transmission and pathogenicity of the virus. A hasty spread of COVID-19 throughout the world is highly threatening, but still, scientists do not have a proper therapeutic measure to fight with it. Scientists are endeavoring across the world to find effective therapy to combat COVID 19. Several drugs such as Remdesivir, Hydroxychloroquine, Chloroquine, Ribavirin, Ritonavir, Lopinavir, Favipiravir, Interferons, Bevacizumab, Azithromycin, etc. are currently under clinical trials. Vaccine development from various pharmaceutical companies and research institutes is under progress, and more than ten vaccine candidates are in the various phases of clinical trials. This review work highlighted the origin, emergence, structural features, pathogenesis, and clinical features of COVID-19. We have also discussed the in-line treatment strategies, preventive measures, and vaccines to combat the emergence of COVID-19.

The aim of this study is to investigate the effects of rapid testing and social distancing in controlling the spread of COVID-19, particularly in the city of Jakarta, Indonesia. We formulate a modified susceptible exposed infectious recovered compartmental model considering asymptomatic individuals. Rapid testing is intended to trace the existence of asymptomatic infected individuals among the population. This asymptomatic class is categorized into two subclasses: detected and undetected asymptomatic individuals. Furthermore, the model considers the limitations of medical resources to treat an infected individual in a hospital. The model shows two types of equilibrium point: COVID-19 free and COVID-19 endemic. The COVID-19-free equilibrium point is locally and asymptotically stable if the basic reproduction number ( R 0 ) is less than unity. In contrast, COVID-19-endemic equilibrium always exists when R 0 > 1 . The model can also show a backward bifurcation at R 0 = 1 whenever the treatment saturation parameter, which describes the hospital capacity, is larger than a specific threshold. To justify the model parameters, we use the incidence data from the city of Jakarta, Indonesia. The data pertain to infected individuals who self-isolate in their homes and visit the hospital for further treatment. Our numerical experiments indicate that strict social distancing has the potential to succeed in reducing and delaying the time of an outbreak. However, if the strict social distancing policy is relaxed, a massive rapid-test intervention should be conducted to avoid a large-scale outbreak in the future.

The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.

Treatment of coronavirus disease 2019 (COVID-19) among patients with CKD requires special pharmacotherapy considerations that are reviewed here. Literature review was done for several pharmacotherapy aspects in CKD patients including selection and modification of COVID-19 treatment, drug interactions, nephrotoxicity of drugs that are used for treatment of COVID-19 and potential risks/benefits of routine medications of CKD patients during COVID-19 pandemic. CKD patients should be treated according to local or national COVID-19 protocols as other patients. But, there is no data on using remdesivir in patients with severe CKD. Oseltamivir and ribavirin require dose modification in patients with moderate to severe CKD. Nephrolithiasis, CKD, and acute interstitial nephritis have been reported with protease inhibitors. Acute kidney injury has been reported with remdesivir in patients with severe COVID-19. Pharmacokinetic-enhanced protease inhibitors increase the concentration of some drugs such as statins, cinacalcet, steroids, calcineurin inhibitors (CNIs). Some hypothetical benefits and harms have been suggested for statins and renin-angiotensinaldosterone system inhibitors in COVID-19 patients. Continuing guideline-directed administration of these drugs is recommended. Among different immunomodulating/immunosuppressive drugs, hydroxychloroquine and CNIs are the safest ones during COVID-19. Antimetabolites are suggested to be withheld during moderate to severe COVID-19. Fluid therapy and anticoagulant prophylaxis/ treatment need special attention in CKD patients with COVID-19. CKD patients with COVID-19 are treated as other patients, with some dose modifications if needed. Be mindful for management of drug interactions as well as modification of immunosuppressive drugs in patients with moderate to severe COVID-19.

BACKGROUND: Mobile health (mHealth) app use is a major concern because of the possible dissemination of misinformation that could harm the users. Particularly, it can be difficult for health care professionals to recommend a suitable app for coronavirus disease (COVID-19) education and self-monitoring purposes. OBJECTIVE: This study aims to analyze and evaluate the contents as well as features of COVID-19 mobile apps. The findings are instrumental in helping health care professionals to identify suitable mobile apps for COVID-19 self-monitoring and education. The results of the mobile apps' assessment could potentially help mobile app developers improve or modify their existing mobile app designs to achieve optimal outcomes. METHODS: The search for the mHealth apps available in the android-based Play Store and the iOS-based App Store was conducted between April 18 and May 5, 2020. The region of the App Store where we performed the search was the United States, and a virtual private network app was used to locate and access COVID-19 mobile apps from all countries on the Google Play Store. The inclusion criteria were apps that are related to COVID-19 with no restriction in language type. The basic features assessment criteria used for comparison were the requirement for free subscription, internet connection, education or advisory content, size of the app, ability to export data, and automated data entry. The functionality of the apps was assessed according to knowledge (information on COVID-19), tracing or mapping of COVID-19 cases, home monitoring surveillance, online consultation with a health authority, and official apps run by health authorities. RESULTS: Of the 223 COVID-19-related mobile apps, only 30 (19.9%) found in the App Store and 28 (44.4%) in the Play Store matched the inclusion criteria. In the basic features assessment, most App Store (10/30, 33.3%) and Play Store (10/28, 35.7%) apps scored 4 out of 7 points. Meanwhile, the outcome of the functionality assessment for most App Store apps (13/30, 43.3%) was a score of 3 compared to android-based apps (10/28, 35.7%), which scored 2 (out of the maximum 5 points). Evaluation of the basic functions showed that 75.0% (n=36) of the 48 included mobile apps do not require a subscription, 56.3% (n=27) provide symptom advice, and 41.7% (n=20) have educational content. In terms of the specific functions, more than half of the included mobile apps are official mobile apps maintained by a health authority for COVID-19 information provision. Around 37.5% (n=18) and 31.3% (n=15) of the mobile apps have tracing or mapping and home monitoring surveillance functions, respectively, with only 17% (n=8) of the mobile apps equipped with an online consultation function. CONCLUSIONS: Most iOS-based apps incorporate infographic mapping of COVID-19 cases, while most android-based apps incorporate home monitoring surveillance features instead of providing focused educational content on COVID-19. It is important to evaluate the contents and features of COVID-19 mobile apps to guide users in choosing a suitable mobile app based on their requirements.

OBJECTIVE: The COVID-19 pandemic has forced healthcare providers worldwide to bring in changes in the way cancer patients are cared for. Many cancer departments globally have brought in changes to their daily practice. This article is about our experience of evolving "COVID 19 PROTOCOL" devised in our department and taking a shape to suit a health care system with limited budget. MATERIALS AND METHODS: All the patient census & details of department of surgical oncology, Royapettah cancer hospital, from month of March 2020 to July 2020, who were subjected to COVID protocol were compared to patient census of similar duration in immediate past five months of October 2019 to February 2020. The data from out-patient department, ward in-patient census and healthcare personnel data was analyzed. RESULTS: There was a drop to 63.5% in OP census and 61.6% in IP census. There was a drop to 64.5% in number of major cases operated during initial phases of COVID pandemic. Health care workers were also infected with the COVID but cross infectivity can be checked if proper steps to adhere to an institutional protocol based on general measures of cleanliness are taken. CONCLUSION: Adherence to an institutional protocol based on compliance to general measures of masking, hand washing and social distancing plays a major role in minimizing disease spread. The Royapettah COVID protocol, though in process of evolution, can be recommended for any health care center with limited resources.

Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) are caused by three distinct coronaviruses belonging to the same genus. COVID-19 and its two predecessors share many important features in their clinical presentations, and in their propensity for progression to severe disease which is marked by high rates of morbidity and mortality. However, comparison of the three viral illnesses also reveals a number of specific differences in clinical manifestations and complications, which suggest variability in the disease process. This narrative review delineates the pulmonary, cardiac, renal, gastrointestinal, hepatic, neurological and hematologic complications associated with these three respiratory coronaviruses. It further describes the mechanisms of immune hyperactivation-particularly cytokine release syndrome-implicated in the multi-organ system injury seen in severe cases of MERS, SARS and COVID-19.

Case identification, isolation, and contact tracing are fundamental strategies used to control the spread of coronavirus disease 2019 (COVID-19). This has led to widespread testing that interrupted the supply chain for testing materials around the world. A prospective study was conducted to compare inexpensive and easily sourced 3-dimensionally (3D)-printed polylactic acid and polyester nasopharyngeal swabs to commercially manufactured swabs for the detection of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). During the study period, 287 laboratory-confirmed hospitalized COVID-19 patients, at multiple stages of their illness, were enrolled. The median age for the study population was 47.6 years (interquartile range [IQR], 34.4 to 56.6 years), and two-thirds (67.6%) of the subjects were male. The median duration of hospitalization, at the time of sampling, was 13 days (IQR, 10 to 16 days). Overall concordance between the prototype and control swabs was 80.8% (Cohen's kappa coefficient, 0.61). Most discrepant results were due to prototype-positive control-negative results. When considering all positive results to be true positives, the prototype swab had a higher sensitivity (90.6% versus 80.8%; 95% confidence interval [CI], 85.7% to 94.0% and 74.7% to 85.7%, respectively; P < 0.015). The cost to produce the prototype swab was estimated to be $0.05 per swab. Polylactic acid 3D-printed polyester-tipped swabs were shown to be effective for nasopharyngeal sample collection. We believe that this design can easily be adopted in countries where commercial swabs are not readily available and can play a vital role in public health efforts for disease control in low-income countries.

INTRODUCTION: Understanding the challenges experienced by pediatric surgeons in the early phases of the pandemic may help identify key issues and focus research. MATERIALS AND METHODS: Two pediatric surgeons from each of the 10 countries most affected by COVID-19 were surveyed over a 10-day period. Data were obtained regarding service provision, infection control, specific surgical conditions, and the surgical workforce. RESULTS: Twenty pediatric surgeons responded. All centers had postponed non-emergency surgery and clinics for nonurgent conditions with virtual consultations being undertaken in 90% of centers. A majority (65%) of centers had not yet knowingly operated on a positive patient. Minimal access surgery was performed in 75% centers but a further 75% had reduced or stopped upper gastrointestinal endoscopy. The management of simple appendicitis was unchanged in 70% centers, patients with intussusception were being referred for radiological reduction in all centers and definitive pull-through surgery for Hirschsprung patients was performed by 95% where washouts were successful. Timing of surgery for reducible neonatal inguinal hernias had changed in 55% of centers and the management of urgent feeding gastrostomy referrals and of inflammatory bowel disease patients failing with biological therapy varied considerably. CONCLUSION: Service provision has been severely affected by COVID-19 leading to an inevitable increase in untreated surgical pathology. Better understanding of extrapulmonary infectivity, the risk of asymptomatic carriage in children, and the reliability of testing for surgical scenarios may allow appropriate use of conventional surgery, including laparoscopy and endoscopy, and rational development of the novel care pathways needed during the pandemic.

Myocardial dysfunction and coronary artery dilation have been reported in the acute setting of severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children. Through a longitudinal echocardiographic single-center study of 15 children, we report the short-term outcomes of cardiac dysfunction and coronary artery dilation in severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children.

This study aims to assess the peripheral blood cell count "signature" of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer-Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden's Index (-0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.

OBJECTIVES: Evaluate the relevance of the coronavirus disease 2019 (COVID-19) positive case detection policy or model implemented by the Ministry of Public Health (MPH) of Ecuador and to compare it with the experiences of other countries. METHODS: Data contained the daily reports publicized by the MPH. The formulations were carried out under the Conditioned Probability modality applying Bayes' Theorem. All the COVID-19 tests applied in relation to the confirmed cases per million inhabitants were considered to obtain their level of positivity, and compared with the experience of Iceland and South Korea. RESULTS: The probability of detecting positive cases of COVID-19 in Ecuador was higher than Iceland and South Korea, because the diagnostic tests were aimed at symptomatic patients, without identifying asymptomatic or mild symptomatic, who play an important role in the transmission of the disease. In addition, many symptomatic patients were examined but will remain undiagnosed due to the unavailability of tests and the low quality of many of them. CONCLUSIONS: The daily reports on the behavior of the COVID-19 issued by the Ecuadorian government do not adequately represent the growth in the number of those infected each day, nor the actual behavior of the epidemic, affecting possible control measures.

As the coronavirus disease 2019 (COVID-19) outbreak has rapidly evolved into a global pandemic, abdominal organ transplantation programs are currently facing multiple challenges. Transplant candidates and recipients are considered high-risk populations for severe disease and death due to COVID-19 as a result of their numerous underlying comorbidities, advanced age and impaired immune function. Emerging reports of atypical and delayed clinical presentations in these patients generate further concerns for widespread disease transmission to medical personnel and the community. The striking similarities between COVID-19 and other outbreaks that took place over the past two decades, like Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, highlight the severity of the situation and dictate that extra measures should be taken by the transplant programs to avoid adverse outcomes. Transplant organizations are currently calling for strict screening and isolation protocols to be established in all transplant programs, for both organ donors and recipients. As the situation escalates, more radical measures might be necessary, including a temporary hold on non-urgent transplantations, resulting in serious ethical dilemmas between the survival of these patients and the safety of the community. Further data about these special populations could result in more individualized guidelines for abdominal organ transplantation in the era of COVID-19.

Understanding the spatio-temporal characteristics or patterns of the 2019 novel coronavirus (2019-nCoV) epidemic is critical in effectively preventing and controlling this epidemic. However, no research analyzed the spatial dependency and temporal dynamics of 2019-nCoV. Consequently, this research aims to detect the spatio-temporal patterns of the 2019-nCoV epidemic using spatio-temporal analysis methods at the county level in Hubei province. The Mann-Kendall and Pettitt methods were used to identify the temporal trends and abrupt changes in the time series of daily new confirmed cases, respectively. The local Moran's I index was applied to uncover the spatial patterns of the incidence rate, including spatial clusters and outliers. On the basis of the data from January 26 to February 11, 2020, we found that there were 11 areas with different types of temporal patterns of daily new confirmed cases. The pattern characterized by an increasing trend and abrupt change is mainly attributed to the improvement in the ability to diagnose the disease. Spatial clusters with high incidence rates during the period were concentrated in Wuhan Metropolitan Area due to the high intensity of spatial interaction of the population. Therefore, enhancing the ability to diagnose the disease and controlling the movement of the population can be confirmed as effective measures to prevent and control the regional outbreak of the epidemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

OBJECTIVE: The exceptional health situation related to the SARS-Cov2 coronavirus pandemic (COVID-19) required a deep and very quickly adaptation of management practices in gynecological cancer. The main objective is to estimate the proportion of patients with treatment modifications. METHOD: This is a multicenter prospective study conducted in 3 university gynecological cancer departments (HCLyon, France) during the period of confinement (March 16 to May 11, 2020). All patients with non-metastatic breast cancer or gynecological cancer were included. The planned treatment, postponement, delay and organizational modifications (RCP, teleconsultations) were studied. RESULTS: Two hundred and five consecutive patients were included, average age 60.5+/-1.0. 7 patients (3.4%) had SARS-Cov-2 infection, 2 patients died. One hundred and twenty-two patients (59.5%) had a treatment maintained, 72 patients (35.1%) postponed, 11 patients (5.4%) cancelled. Of the 115 (56.1%) planned surgeries, 40 (34.8%) postponed, 7 cancelled (6.1%). 9 patients (7.8%) had a surgical modification. Of the 59 (28.8%) radiotherapy treatments scheduled, 24 (40.7%) postponed and 2 (3.4%) cancelled. Of the 56 (27.3%) chemotherapy treatment planned, 8 (14.3%) postponed and 2 (3.6%) cancelled. One hundred and forty-five patients (70.7%) have been discussed in multidisciplinary meeting. One hundred and fifty-eight patients (77%) had a teleconsultation system. CONCLUSION: Our study assessed the impact of the COVID-19 pandemic on therapeutic management of patients with gynecological cancer during the period of confinement. This will probably improve our management of an eventual epidemic rebound or future health crisis.

The coronavirus disease 2019 (COVID-19) pandemic is straining the healthcare system, particularly for patients with severe outcomes requiring admittance to the intensive care unit (ICU). This study investigated the potential associations of obesity and diabetes with COVID-19 severe outcomes, assessed as ICU admittance. Medical history, demographic and patient characteristics of a retrospective cohort (1158 patients) hospitalized with COVID-19 were analysed at a single centre in Kuwait. Univariate and multivariate analyses were performed to explore the associations between different variables and ICU admittance. Of 1158 hospitalized patients, 271 had diabetes, 236 had hypertension and 104 required admittance into the ICU. From patients with available measurements, 157 had body mass index (BMI) >/=25 kg/m(2) . Univariate analysis showed that overweight, obesity class I and morbid obesity were associated with ICU admittance. Patients with diabetes were more likely to be admitted to the ICU. Two models for multivariate regression analysis assessed either BMI or diabetes on ICU outcomes. In the BMI model, class I and morbid obesities were associated with ICU admittance. In the diabetes model, diabetes was associated with increased ICU admittance, whereas hypertension had a protective effect on ICU admittance. In our cohort, overweight, obesity and diabetes in patients with COVID-19 were associated with ICU admittance, increasing the risk of poor outcomes.

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called "cytokine storm"), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

Nicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD(+) ) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis. Plus, NAD acts as a signalling molecule, being a cosubstrate for several enzymes such as sirtuins, poly-ADP-ribose-polymerases (PARPs) and some ectoenzymes like CD38, regulating critical biological processes like gene expression, DNA repair, calcium signalling and circadian rhythms. Given the large number of mitochondria present in cardiac tissue, the heart has the highest NAD levels and is one of the most metabolically demanding organs. In several models of heart failure, myocardial NAD levels are depressed and this depression is caused by mitochondrial dysfunction, metabolic remodelling and inflammation. Emerging evidence suggests that regulating NAD homeostasis by NAD precursor supplementation has therapeutic efficiency in improving myocardial bioenergetics and function. This review provides an overview of the latest understanding of the different NAD biosynthesis pathways, as well as its role as a signalling molecule particularly in cardiac tissue. We highlight the significance of preserving NAD equilibrium in various models of heart diseases and shed light on the potential pharmacological interventions aiming to use NAD boosters as therapeutic agents.

The pandemic from the SARS-CoV2 Virus is currently challenging health care systems all over the world. Maintaining appropriate staffing and resources in healthcare facilities is essential to guarantee a safe work environment for healthcare personnel and safe patient care. Extracorporeal membrane oxygenation (ECMO) represents a valuable therapeutic option in patients with severe heart or lung failure. Although only a limited proportion of COVID-19 patients develops respiratory or circulatory failure that is refractory to conventional therapies, it is of utmost importance to clearly define criteria for the use of ECMOs in this steadily growing patient population. The ECMO working group of the Medical University of Vienna has established the following recommendations for ECMO support in COVID-19 patients.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.

OBJECTIVES: While numerous medical facilities have been forced to suspend oncological surgery due to system overload, debate has emerged on using non-surgical options on cancer cases during the pandemic. The goal of our study was to analyze, in a retrospective cohort study, the results of gynecological cancer surgery and evaluate postoperative complications in a single center in one of the most affected areas in Europe. METHODS: We retrospectively analyzed the records of patients who were referred between March 2020 and May 2020 for primary surgical treatment of breast, endometrial, ovarian, cervical, or vulvar cancer. RESULTS: The study included a total of 126 patients. Median age was 60 years (range 29-89). Patients were referred with breast (76/126, 60.3%), endometrial (29/126, 23%), ovarian (14/126, 11.1%), cervical (5/126, 4%), or vulvar cancer (2/126, 1.6%). Polymerase chain reaction (PCR) test for detection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was only conducted in 50% of cases due to the low availability of tests during the first phase of our study, and was indicated only in suspected cases according to the healthcare authorities' protocol. Median hospital stay was 1 day (range 0-18). Excluding breast surgery, laparoscopy was the most used procedure (43/126, 34.1%). 15 patients had a postoperative complication (15/126, 11.9%); only in 2 patients (2/15 13.3%) were there reports of Clavien-Dindo grade 3 or 4 complications. 6 patients tested positive for COVID-19 following a PCR diagnostic test, and these surgeries were cancelled. CONCLUSIONS: Adequate protective measures in the setting of COVID-19 free institutions enabled the continuity of cancer surgery without significant compromise of the safety of patients or healthcare workers.

The present study investigates the differences in inflammatory agents alterations, immune function, and leukocyte differential count evaluation in severe pneumonia of SARS-COV-2 patients with Yidu-toxicity blocking lung syndrome after the recommended Chinese medicine prescription of Yidu-toxicity blocking lung decoction. A total of 40 patients with yidu-toxicity blocking lung syndrome, diagnosed as severe pneumonia of SARS-COV-2 following the latest Chinese national recommendations for the diagnosis and treatment of pneumonia caused by SARS-COV-2 (the 5th edition), were recruited. They were randomly divided into the pure western medicine therapy group (PWM) and integrated into Chinese and Western medicine therapy group (ICW). The general strategies were given to both groups according to the national recommendations, and the ICW group was given Yidu-toxicity blocking lung decoction extraorally. A radioimmunoassay method was adopted to detect the content of IL-6, IL-8,IL-2R,TNF-alpha, procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in sera. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD3+, CD4+, CD8+, and the ratios of CD4+/CD8+). The white blood cell counts (WBC#), neutrophils count(N#), and lymphocyte counts (L#) were measured using a fully automatic blood rheological instrument. The t-test or Rank Sum Test and Spearman analysis were conducted to evaluate the differences. The results showed that IL-6 (P = 0.013) and TNF-alpha (P = 0.035) levels in the PWM group were significantly higher than those in the ICW group after treatment. Infection related indicators such as WBC#, N#, L#, hs-CRP showed no differences. The analysis showed that there was no statistical difference in the values of CD4 and CD8 between the two groups. By the end of Day 29, all patients were discharged and the final cure rate for both group were 100 %. Taken together, we conclude that Yidu-toxicity blocking lung decoction could relieve inflammation of SARS-COV-2 patients with yidu-toxicity blocking lung syndrome by eliminating inflammatory agents. CM can serve as a complementary medication to western medicine, which should be highlighted in clinical settings.

Coronavirus disease 2019 is an active pandemic that has required rapid conversion of practice patterns to mitigate disease spread. Although recommendations have been released for physicians to postpone elective procedures, the utility of common physiatry procedures and their infectious risk profile have yet to be clearly delineated. In this article, we describe an update on existing national recommendations and outline considerations as practitioners and institutions strive to meet the needs of patients with disabilities.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.

Brazil is, at the time of writing, the global epicenter of COVID-19, but information on risk factors for hospitalization and mortality in the country is still limited. Demographic and clinical data of COVID-19 patients until June 11th, 2020 were retrieved from the State Health Secretariat of Espirito Santo, Brazil. Potential risk factors for COVID-19 hospitalization and death were analyzed by univariate and multivariable logistic regression models. A total of 10,713 COVID-19 patients were included in this study; 81.0% were younger than 60 years, 55.2% were female, 89.2% were not hospitalized, 32.9% had at least one comorbidity, and 7.7% died. The most common symptoms on admission were cough (67.7%) and fever (62.6%); 7.1% of the patients were asymptomatic. Cardiovascular diseases (23.7%) and diabetes (10.3%) were the two most common chronic diseases. Multivariate logistic regression analysis identified an association of all explanatory variables, except for cough and diarrhea, with hospitalization. Older age (odds ratio [OR] = 3.95, P < 0.001) and shortness of breath (OR = 3.55, P < 0.001) were associated with increase of odds to COVID-19 death in hospitalized patients. Our study provided evidence that older age, male gender, Asian, indigenous or unknown race, comorbidities (smoking, kidney disease, obesity, pulmonary disease, diabetes, and cardiovascular disease), as well as fever and shortness of breath increased the risk of hospitalization. For death outcome in hospitalized patients, only older age and shortness of breath increased the risk.

BACKGROUND: The use of shared ventilation, or the simultaneous support of multiple patients connected in parallel to a single mechanical ventilator, is receiving considerable interest for addressing the severe shortage of mechanical ventilators available during the novel coronavirus pandemic (COVID-19). In this paper we highlight the potentially disastrous consequences of naive shared ventilation, in which patients are simply connected in parallel to a ventilator without any regard to their individual ventilatory requirements. We then examine possible approaches for individualization of mechanical ventilation, using modifications to the breathing circuit that may enable tuning of individual tidal volumes and driving pressures during either volume-controlled ventilation (VCV) or pressure-controlled ventilation (PCV). METHODS: Breathing circuit modifications included a PEEP valve on each expiratory limb for both VCV and PCV, an adjustable constriction and one-way valve on the inspiratory limb for VCV, and a pressure-relief valve for peak inspiratory pressure reduction on the inspiratory limb for PCV. The ability to regulate individual tidal volumes using these breathing circuit modifications was tested both theoretically in computer simulations as well as experimentally in mechanical test lungs. RESULTS: In both the simulations and experimental measurements, naive shared ventilation resulted in large imbalances across individual tidal volume delivery, dependent on imbalances across patient mechanical properties. The proposed breathing circuit modifications for shared VCV and shared PCV enabled optimization of tidal volume distributions. Individual tidal volume for one patient during shared VCV was sensitive to changes in the mechanical properties of other patients. By contrast, shared PCV enabled independent control of individual patient-received ventilation. CONCLUSIONS: Of the shared ventilation strategies considered, shared PCV, with the inclusion of in-line pressure-relief valves in the individual inspiratory and expiratory limbs, offers the greatest degree of safety and lowest risk of catastrophic mechanical interactions between multiple patients connected to a single ventilator.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most significant global health crisis of the 21st century. The aim of this study was to develop a model to simulate the effect of undocumented infections, seasonal infectivity, immunity, and non-pharmaceutical interventions (NPIs) on the transmission, morbidity, and mortality of SARS-CoV-2 in New York State (NYS) based on data collected between March 4 and April 28, 2020. Simulations predict that undocumented infections significantly contribute to infectivity, NPIs are effective in reducing morbidity and mortality, and relaxation >50% of NPIs from initial lock-down levels may result in tens-of-thousands more deaths. Endemic infection is likely to occur in the absence of sustained immunity. As a result, until an effective vaccine or other effective pharmaceutical intervention is developed, the risks of significantly reducing NPIs should be carefully considered. This study employs modelling to simulate fundamental characteristics of SARS-CoV-2 transmission, which can help policymakers navigate combating this virus in the coming years.

AIM: Contact lens wearers need to maintain optimal hygiene practices during the COVID-19 pandemic to minimise contact-lens complications including microbial keratitis and corneal infiltrative events. This online survey (UK and Ireland) explored contact lens wearers' compliance behaviours, attitudes and concerns during the pandemic. METHOD: The 60-item anonymous online survey was distributed during a 1-month period via Qualtrics (starting on 14/04/20). The survey captured: a) demographic information, b) type of lenses worn and compliance with lens wear and care procedures, c) adherence to recommendations and d) concerns associated with contact lens wear during the pandemic. RESULTS: Two hundred and forty seven responses were received (34.3+/-11.7 years old, 79% female). Seventy nine percent of participants reported that they were self-isolating or rigorously following social distance advice. Fifty-six percent of participants reported using their lenses less during the pandemic. Eighty-seven percent of respondents reported following the recommended 20-second rule most times/every time and 96% used soap and water during handwashing. Eleven percent of respondents admitted not following recommendations regarding disposal of lenses and 18% would not consider ceasing lens wear if unwell (with flu/cold) during the pandemic. CONCLUSION: Respondents reported wearing their contact lenses less than usual. Good compliance with handwashing was observed but soft reusable lens wearers showed a statistically significant lower compliance with lens wear and care compared to daily disposable lens wearers (p=<0.001).

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5 degrees C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 10(9) cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters alpha = 0.05 (2-sided), power: 1-beta = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

COVID-19 pandemic has become a global concern. Cytokine release syndrome (CRS) complicates acute respiratory distress syndrome (ARDS) and causes multi-organ failure which can subsequently lead to mortality in COVID-19 patients. Tocilizumab, an interleukin-6 antagonist, has shown to salvage patients with cytokine release storm. In this study, we aim to evaluate therapeutic response of Tocilizumab in COVID-19 patients. A single-arm retrospective review of 40 patients with COVID-19, admitted to The Aga Khan University Hospital Karachi, from March 2020 to May 2020 was performed. Selection of patients for use of Tocilizumab was based on severity of disease, rapid clinical deterioration, presence of CRS and absence of any absolute contraindication to Tocilizumab. Improvement after Tocilizumab was defined as improvement in oxygen requirement and inflammatory parameters. Serum levels of inflammatory cytokines like C-reactive protein, ferritin, D-dimer and lactate dehydrogenase levels were monitored before and after administering Tocilizumab. Mean age was 62.4 years and 33 (82.5%) were male. 19 (47.5%) patients were critically sick, 18 (45%) were severely sick and 3 (7.5%) were moderately sick. 29 (77.5%) patients showed significant improvement in oxygen requirement, inflammatory parameters and chest x-rays, out of which 28 patients were discharged home. The mean duration between administration of Tocilizumab and overall improvement was 4.3 +/- 3.2 days. Hence, Tocilizumab can be used as a possible treatment option in patients with COVID-19 induced CRS but needs monitoring for its adverse effects.

The global spread of coronavirus disease 2019 (COVID-19) is rapidly increasing the number of patients who are critically ill with this disease, with the related rate of mortality expected to peak in 2020 (Alhazzani et al., 2020). As severe acute respiratory syndrome is the major cause of mortality after COVID-19 infection, patients with COVID-19 who are prone to severe acute respiratory problems may require mechanical ventilation or extracorporeal membrane oxygenation (ECMO; Alhazzani et al., 2020). Ongoing advances in intensive care medicine are continuing to improve survival in critically ill patients (Kaukonen, Bailey, Suzuki, Pilcher, & Bellomo, 2014). However, intensive care unit (ICU) survivors may experience complications and problems related to their disease and treatment such as critical illness polyneuropathy, critical illness myopathy, and post intensive care syndrome (PICS; Alhazzani et al., 2020). Harvey (2012) reported that 85%-95% of ICU patients have ICU-acquired weakness after ICU discharge and 74% of ICU patients with acute respiratory distress syndrome have cognitive impairment after ICU discharge. Physical disabilities, cognitive impairment, and mental or psychological distress (e.g., anxiety, depression, and post-traumatic stress disorder) after ICU discharge may be symptoms of PICS, and may continue to affect surviving patients for several years after ICU discharge (Elliott et al., 2014; Held & Moss, 2019; Jackson et al., 2014; Jubran et al., 2010). Efforts to prevent and treat COVID-19 in Taiwan have proven more effective compared to most other places in the world. In addition to the low number of diagnosed cases, the mortality rate (seven of 440 confirmed cases) in Taiwan has been significantly lower than in most other countries (Taiwan Centers for Disease Control, ROC, 2020, May 14). However, post-discharge care for ICU survivors, especially those hospitalized after a sudden onset of severe disease symptoms and then discharged after a long ICU stay or after receiving mechanical ventilation, require specialized care to minimize PICS. Nurses are responsible not only for treating patients with the disease but also for preventing the further spread of disease. Therefore, providing continued care to patients discharged from the ICU is essential. Specifically, interventions to avoid PICS must be implemented rapidly by multidisciplinary medical teams during and immediately after ICU discharge.

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.

OBJECTIVE: The aims of this study were to follow up the monitoring, health and anxiety from women who became pregnant after an embryo transfer or a intrauterine insemination during the COVID-19 epidemic in France STUDY DESIGN: This is a single centre, retrospective study from December 2019 to March 2020 based on a phone call interview using a specific questionnaire sheet specially developed for this study. Questionnaires from 104 pregnant women were completed and descriptive data are then analyzed. RESULTS: Women with ongoing pregnancies (n=88) did not change their physician visits. The COVID-19 outbreak has created no or few additional stresses for 77 % of pregnant women since the lockdown started. We report a miscarriage rate of 14.4 % (n=15) and documented 10 patients (11.3 %) who had symptoms related to COVID-19. No severe symptoms and no hospitalization in intensive care unit were identified. CONCLUSION: The epidemic context did not disrupt the medical monitoring of pregnancies and we did not recover an increased rate of miscarriage after ART. None of the patients who had COVID-related symptoms presented with severe clinical manifestations. Surprisingly, pregnant women were psychologically able to experience the lockdown.

A 48-year-old woman with a past medical history of migraines and hyperlipidemia presented due to severe retrosternal chest pain with no other associated signs or symptoms. The patient was hemodynamically stable and was found to have an elevated troponin with electrocardiogram showing no ischemic changes. Computed tomography of the coronary arteries showed a left dominant system with dissection extending from the mid-to-distal left anterior descending (LAD) artery. The patient was subsequently discharged on medical therapy but returned 3 days later due to worsening chest pain. Electrocardiogram revealed inferior and anteroseptal ST segment changes with peak troponin of 14.9 ng/ml (reference range <0.80 ng/ml). Coronavirus disease 2019 (COVID-19) nasopharyngeal swab was performed prior to urgent coronary angiogram. Coronary angiogram was performed with full personal protective equipment for respiratory and droplet precautions due to pending COVID-19 testing results. Angiogram revealed spontaneous coronary artery dissection (SCAD) extending from the ostium of the LAD to the distal vessel. COVID-19 testing returned positive while in intensive care unit. The patient was not a percutaneous coronary intervention candidate due to the extent of the dissection and was not a surgical candidate due to a lack of graftable target and medical management was continued. To our knowledge, this case is the first in which SCAD has been reported in the LAD in a patient with COVID-19 with no other symptoms of respiratory illness or symptoms classically associated with the novel coronavirus. SCAD should be considered on the differential as one of the various cardiac manifestations of COVID-19 infection.

OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with coronavirus disease 2019 (COVID-19). STUDY DESIGN: Children 1 month to 21 years of age with COVID-19 from a single tertiary care children's hospital between March 15 and April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: In total, 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (P = .99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (P < .05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (P = .0001) and were more likely to have received Remdesivir through compassionate release (P < .05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) patients in the PICU. Acute respiratory distress syndrome was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.

BACKGROUND: The COVID-19 pandemic has impacted adults with chronic diseases, and their health care delivery. Patterns of COVID-19-related preventive behaviors practiced by cancer survivors are unknown, including practices related to canceling doctor's appointments. We evaluated COVID-19-related preventive behaviors among cancer survivors in the United States. METHODS: We used nationally representative data of 10,760 U.S. adults from the COVID-19 Impact Survey. We defined cancer survivors as those with a self-reported diagnosis of cancer (n = 854, 7.6%). We present frequencies and chi(2) tests to evaluate COVID-19-related preventive behaviors among cancer survivors. We estimated determinants of canceling doctor's appointments among cancer survivors using Poisson regression models. RESULTS: Cancer survivors were more likely to practice preventive behaviors, including social distancing (93%, chi(2) P < 0.001), wearing a face mask (93%, chi(2) P < 0.001), and avoiding crowded areas (84%, chi(2) P < 0.001) compared with adults without cancer. Cancer survivors were more likely to cancel doctor's appointments (41%, chi(2) P < 0.001), whereas they were less likely to cancel other social activities such as work (19%, chi(2) P < 0.001) and school-related (13%, chi(2) P < 0.001) activities. After adjustment for covariates, while non-Hispanic (NH)-Black cancer survivors were less likely to cancel a doctor's appointment compared with NH-White cancer survivors, cancer survivors aged 18 to 29, who were female, and who had least one comorbid condition were more likely. CONCLUSIONS: Cancer survivors are adhering to recommended preventive behaviors. Cancer survivor's continuity of care may be impacted by COVID-19, specifically young adults, females, and those with existing comorbid conditions. IMPACT: Insights into cancer survivors whose care may be most impacted by COVID-19 will be valuable toward surveillance and survivorship of U.S. cancer survivors.

BACKGROUND: The extreme social circumstances caused by declared COVID-19 pandemic deeply intervene people's everyday life and should not be neglected but seen through the view of social reality pinpointing the 'ordinary' people. In this article, authors explored basic segments of everyday and their subjective perception to what extent sleeping habits, physical inactivity, physical activity, nutritional habits and smoking have changed. METHODS: The online survey was conducted in nine European countries (Bosnia and Herzegovina, Croatia, Greece, Kosovo*, Italy, Serbia, Slovakia, Slovenia and Spain) in 4108 participants, aged 15-82 years. The survey took place 30-40 days after World Health Organization declared COVID-19 pandemic state, from 15 April to 3 May 2020. RESULTS: The results have shown 30 min longer sleeping time, 50% longer physical inactivity time, 65% longer screen time, 43% shorter walking time, 24% shorter sport time and 37% longer physical work time. Additionally, body mass gains (0.3 kg) could be explained in 20.6% with meals sizes, unhealthy food consumption, screen time and sport time. Further, respondents reported more regular meals (44%) and healthier meals with less alcohol consumption and less smoking, which have been positive outcomes of home confinement. CONCLUSION: The findings draw attention to negative changes in everyday praxis (inactivity, body mass gain) after such a short period. Because of possible risk to population's health (especially of countries such as Italy and Spain with serious threat and more stringent measures), findings enable development of recommendations for maintaining healthy lifestyle habits with minimal negative health consequences in similar pandemic circumstances.

OBJECTIVE: To determine the cardiotocograph (CTG) changes in women with symptomatic COVID-19 infection. STUDY DESIGN: 12 anonymised CTG traces from 2 hospitals in Spain were retrospectively analysed by 2 independent assessors. CTG parameters were studied based on fetal pathophysiological responses to inflammation and hypoxia that would be expected based on the pathogenesis of COVID-19 patients. Correlation was made with perinatal outcomes (Apgar score at 5 min and umbilical cord pH). RESULTS: All fetuses showed an increased baseline FHR > 10 percent compared to the initial recording, in addition to absence of accelerations. 10 out of 12 CTG traces (83.3 percent) demonstrated late or prolonged decelerations and 7 out of 12 fetuses (58.3 percent) showed absence of cycling. Not a single case of sinusoidal pattern was observed. ZigZag pattern was found in 4 CTG traces (33 percent). Excessive uterine activity was observed in all CTG traces where uterine activity was monitored (10 out of 12). Apgar scores at 5 min were normal (>7) and absence of metabolic acidosis was found in the umbilical cord arterial pH (pH > 7.0) in the cases that were available (11 and 9, respectively). CONCLUSION: Fetuses of COVID-19 patients showed a raised baseline FHR (>10 percent), loss of accelerations, late decelerations, ZigZag pattern and absence of cycling probably due to the effects of maternal pyrexia, maternal inflammatory response and the "cytokine storm". However, the perinatal outcomes appear to be favourable. Therefore, healthcare providers should optimise the maternal environment first to rectify the reactive CTG changes instead of performing an urgent operative intervention.

Singapore, one of the first countries affected by COVID-19, adopted a national strategy for the pandemic which emphasised preparedness through a whole-of-nation approach. The pandemic was well contained initially until early April 2020, when there was a surge in cases, attributed to Singapore residents returning from hotspots overseas, and more significantly, rapid transmission locally within migrant worker dormitories. In this paper, we present the response of Singapore to the COVID-19 pandemic based on core dimensions of health system resilience during outbreaks. We also discussed on the surge in cases in April 2020, highlighting efforts to mitigate it. There was: (1) clear leadership and governance which adopted flexible plans appropriate to the situation; (2) timely, accurate and transparent communication from the government; (3) public health measures to reduce imported cases, and detect as well as isolate cases early; (4) maintenance of health service delivery; (5) access to crisis financing; and (6) legal foundation to complement policy measures. Areas for improvement include understanding reasons for poor uptake of government initiatives, such as the mobile application for contact tracing and adopting a more inclusive response that protects all individuals, including at-risk populations. The experience in Singapore and lessons learnt will contribute to pandemic preparedness and mitigation in the future.

Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.

We report a case of a 50-year-old male with a history of HIV and kidney transplant who presented with SARS-CoV-2. We also present a review of COVID-19 cases in kidney transplant recipients.

A virus-laden particle movement from urinal flushing is simulated. Similar to the toilet-induced flushing, results indicate that the trajectory of the particles triggered by the urinal flushing manifests an external spread type. Even more alarmingly, the particle can reach 0.84 m (man's thigh) in 5.5 s when compared with the diffusion performance of the toilet-induced one (around 0.93 m in 35 s). A more violent climbing tendency is discovered in this Letter. Wearing masks should be made mandatory in public washrooms, and anti-diffusion improvements of facilities in public washrooms are urgently needed, especially in the current "SARS-CoV-2" crisis.

The coronavirus disease 2019 (COVID-19) pandemic has left the world in a state of desolation with overburdening public health systems in a short period. Finding possible preventative and therapeutic measures to counter severe respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has been the priority. A possible solution is convalescent blood products (CBP), primarily convalescent plasma (CP) and immunoglobulins, as an adjunctive therapy. CBP has been tried on the previous coronavirus epidemics with severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Therefore, we reviewed the clinical utility of CBP and available evidence in COVID-19. We found some of the current anecdotal studies demonstrate promising therapeutic potential, but many of these studies do not meet the academic rigours to substantiate its use with confidence. However, the compassionate use of CBP in critically ill COVID-19 patients can be an option while we await a definitive answer from ongoing randomised clinical trials.

(1) Background: The five rights of clinical decision support (CDS) are a well-known framework for planning the nuances of CDS, but recent advancements have given us more options to modify the format of the alert. One-size-fits-all assessments fail to capture the nuance of different BestPractice Advisory (BPA) formats. To demonstrate a tailored evaluation methodology, we assessed a BPA after implementation of Storyboard for changes in alert fatigue, behavior influence, and task completion; (2) Methods: Data from 19 weeks before and after implementation were used to evaluate differences in each domain. Individual clinics were evaluated for task completion and compared for changes pre- and post-redesign; (3) Results: The change in format was correlated with an increase in alert fatigue, a decrease in erroneous free text answers, and worsened task completion at a system level. At a local level, however, 14% of clinics had improved task completion; (4) Conclusions: While the change in BPA format was correlated with decreased performance, the changes may have been driven primarily by the COVID-19 pandemic. The framework and metrics proposed can be used in future studies to assess the impact of new CDS formats. Although the changes in this study seemed undesirable in aggregate, some positive changes were observed at the level of individual clinics. Personalized implementations of CDS tools based on local need should be considered.

In Japan, the first case of COVID-19 in dialysis patients was reported on March 1, 2020. A total of 31 cases were reported by April 10, and it increased to 95 by May 15. Thereafter, with the rapid increase in the number of COVID-19 cases in the general population since late March, there was a not surprising increase in the number of COVID-19 cases in dialysis patients. The mortality rate is 16.2% (16/99 cases) in dialysis patients, which is higher than 5.3% (874/16 532 cases) in the general population. This higher mortality rate in dialysis patients with COVID-19 might be related to their age; the majority of COVID-19 cases are aged between 70 and 90 years old in dialysis patients, compared with between 20 and 60 years old in the general population. As COVID-19 presents with severe symptoms and is associated with a high mortality rate in dialysis patients, dialysis patients who have contracted severe acute respiratory syndrome coronavirus 2 infection confirmed by polymerase chain reaction testing are required to be hospitalized under Japanese government policy. In cases of COVID-19 hospitalizations, it is essential to prevent nosocomial infection. Therefore, patients must be sufficiently instructed in infection prevention and robust measures to prevent contraction and spread of the infection must be taken at dialysis facilities.

BACKGROUND: In this paper, the authors review the safety and practicality of elastomeric respirators for protecting themselves and others from the novel coronavirus or COVID-19. They also describe the safe donning and doffing procedures for this protective gear. MAIN TEXT: Due to the shortage of personal protective equipment (PPE), the CDC has recommended ways to conserve disposable N95 masks, including re-use and extended use, and reserving N95 masks for aerosol-generating procedures. However, these were never made to be re-used. Although the modes of transmission of COVID-19 are not fully understood, based on what we know about severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), droplets and aerosolized droplets contribute to the spread of this virus. More evidence from Wuhan, China, has demonstrated that COVID-19 viral particles are aerosolized and found in higher concentrations in rooms where PPE is being removed. Thus, it is best for all healthcare providers to have full aerosol protection. CONCLUSION: Given the shortage of PPE for aerosols, it is logical to utilize reusable elastomeric respirators with filter efficiency of 95% or higher. A single elastomeric respirator may replace hundreds to thousands of new disposable N95 masks.

INTRODUCTION: A covid-19 pandemic decreed by WHO has raised greater awareness of it. EPIDEMIOLOGY: The infection, reached the mark of 2,000,000 patients in 33 countries and caused the risk of the presence of comorbidities and advanced age. TRANSMISSIBILITY: The transmissibility calculated so far is similar to the H1N1 epidemic, but with lower mortality rates. PHYSIOPATHOLOGY: The SARS-CoV-2 virus, of the Coronaviridae family, has the capacity for cellular invasion through the angiotensin-converting enzyme 2 does not have a lower respiratory epithelium and in the cells of the small intestine mucosa. CLINICAL MANIFESTATIONS: a presentation can be divided into mild (fever, fatigue, cough, myalgia, and sputum) and severe (cyanosis, dyspnoea, tachypnea, chest pain, hypoxemia and need for clinical measurement) and has an estimated estimate of 2%. DIAGNOSIS: allows the detection of viral load in CRP-TR of patients with high clinical suspicion. TREATMENT: based on supportive measures and infection control. In severe cases, the use of medications such as hydroxychloroquine and azithromycin or medication can be promising. Take care to avoid the use of corticosteroids. There are no restrictions on the use of resources and IECAs / BRAs.

The virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic known as coronavirus disease 2019 (COVID-19) with severe respiratory illness as the predominant manifestation. Neurologic complications from COVID-19 were reported in the early stages of the pandemic and are now increasingly recognized. These include various symptoms like headache and anosmia as well as neurologic complications of severe COVID-19 like encephalopathy, seizures, and stroke. There are few reports of direct involvement of the central nervous system with SARS-CoV-2 causing meningoencephalitis. There is concern for higher incidence and severity of COVID-19 in patients with chronic neurologic conditions. Here, we review the emerging literature along with our anecdotal experience in regard to these neurologic manifestations in patients with COVID-19 and detail the putative pathophysiologic mechanisms for the same.

Background: The concerns of the highly contagious and morbid nature of Coronavirus Disease-2019 (COVID-2019) have prompted healthcare workers to implement strict droplet and contact isolation precautions. Unfortunately, some patients who may be or presumptively or confirmed as infected with COVID-2019 may also require emergent surgical procedures. As such, given the high-risk for exposure of many healthcare workers involved the complex requirements for appropriate isolation must be adhered to. Case presentation: We present our experience with a 77-year-old who required emergency cardiac surgery for a presumed acute aortic syndrome in the setting of a presumed, and eventually confirmed, COVID-2019 infection. We outline the necessary steps to maintain strict isolation precautions to limit potential exposure to the surgical Team. Conclusions: We hereby provide our algorithm for emergent surgical procedures in critically-ill patients with presumptive or confirmed infection with COVID-2019. The insights from this case report can potentially be templated to other facilities in order to uphold high standards of infection prevention and patient safety in surgery during the current COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine.

Objective: To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. Methods: We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. Results: There were 53 males and 42 females, aged 22-84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. Conclusions: COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.

BACKGROUND: At the end of 2019, a novel coronavirus (COVID-19) was identified in China. The high potential of human-to-human transmission led to subsequent COVID-19 global pandemic. Public health strategies including reduced social contact and lockdown have been adopted in many countries. Nonetheless, social distancing and isolation could also represent risk factors for mental disorders, resulting in loneliness, reduced social support and under-detection of mental health needs. Along with this, social distancing determines a relevant obstacle for direct access to psychiatric care services. The pandemic generates the urgent need for integrating technology into innovative models of mental healthcare. AIMS: In this paper, we discuss the potential role of telepsychiatry (TP) and other cutting-edge technologies in the management of mental health assistance. We narratively review the literature to examine the advantages and risks related to the extensive application of these new therapeutic settings, along with the possible limitations and ethical concerns. RESULTS: Telemental health services may be particularly feasible and appropriate for the support of patients, family members and healthcare providers during this COVID-19 pandemic. The integration of TP with other technological innovations (eg, mobile apps, virtual reality, big data and artificial intelligence (AI)) opens up interesting future perspectives for the improvement of mental health assistance. CONCLUSION: Telepsychiatry is a promising and growing way to deliver mental health services but is still underused. The COVID-19 pandemic may serve as an opportunity to introduce and promote, among numerous mental health professionals, the knowledge of the possibilities offered by the digital era.

Background: The current COVID-19 pandemic has changed many medical practices in order to provide additional protection to both our patients and healthcare providers. In many cases this includes seeing patients through electronic means such as telehealth or telephone rather than seeing them in person. Asthma exacerbations cannot always be treated in this way. Problem: Current emergency unit asthma guidelines recommend bronchodilators be administered by metered dose inhaler (MDI) and spacer for mild-moderate asthma and include it as a choice even in severe asthma, but many emergency units continue to prefer nebulised therapy for patients who urgently require beta-agonists. The utilization of nebulised therapy potentially increases the risk of aerosolization of the coronavirus. Since nosocomial transmission of respiratory pathogens is a major threat in the context of the SARS-CoV-2 pandemic, use of nebulised therapy is of even greater concern due to the potential increased risk of infection spread to nearby patients and healthcare workers. Practical implications: We propose a risk stratification plan that aims to avoid nebulised therapy, when possible, by providing an algorithm to help better delineate those who require nebulised therapy. Protocols that include strategies to allow flexibility in using MDIs rather than nebulisers in all but the most severe patients should help mitigate this risk of aerosolised infection transmission to patients and health care providers. Furthermore, expedient treatment of patients with high dose MDI therapy augmented with more rapid initiation of systemic therapy may help ensure patients are less likely to deteriorate to the stage where nebulisers are required.

BACKGROUND: COVID-19 due to SARS-CoV-2 was first described in the city of Wuhan in China and spread around the world turning into a pandemic. COVID-19 can affect different organ systems, including the oral mucosa. AIMS: Although cutaneous involvement has been defined in association with COVID-19, the number of case reports about mucosal involvement by SARS-CoV-2 is limited. Hereby, we report a case of hemorrhagic necrosis on the lip in a patient with paroxysmal nocturnal hemoglobinuria (PNH) and COVID-19 infection and briefly discuss its possible mechanism. PATIENTS: The clinical features and causes of hemorrhagic necrosis on the lip in a woman are presented. RESULTS: In our patient, we think that PNH-associated dermal micro-occlusions caused extensive painful necrosis of the lip. Additionally, COVID-19-induced endothelial damage helped to develop exaggerated hemorrhagic necrosis. CONCLUSION: This current case presentation will contribute to the literature as another case with COVID-19 triggering mucosal involvement.

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

BACKGROUND: The World Health Organization declared on March 11, 2020, that the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has escalated from epidemic into pandemic. As the initial outbreak area, China has taken multiple active measures to deal with the epidemic. Updated versions of diagnosis and treatment guideline for novel coronavirus (COVID-19) patients have been issued, and traditional Chinese herbal medicine has been recommended as a treatment. The objective of this study will be to summarize the recommendations in current clinical practice guidelines about the use of traditional Chinese herbal medicine for COVID-19 patients. We will also evaluate and report on the methodological and reporting quality of these guidelines. METHODS: In this systematic review, we will search for guidelines, expert consensuses, and policy documents published since December 2019 in electronic databases (e.g., PubMed, EMBASE, and Chinese databases) and on websites of governments or organizations (e.g., The National Guideline Clearinghouse [NGC], Guidelines International Network [GIN], National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network [SIGN], and WHO). Eligible documents will be independently selected, and relevant data will be independently extracted by two reviewers. We will also independently evaluate the methodological quality and reporting quality of the included guidelines, using the Appraisal of Guidelines for REsearch & Evaluation (AGREE) II tool and Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement, respectively. Any discrepancies will be discussed and resolved through discussion among the reviewers. We will use the extracted information to summarize their recommendations for traditional Chinese herbal formulae and Chinese patent medicine for COVID-19 patients and to summarize the strength and quality of these recommendations with reference to the results of AGREE II and RIGHT tools. DISCUSSION: This review will summarize the recommendations in current clinical practice guidelines and provide insight into the implementation strategies for traditional Chinese herbal medicine in COVID-19 patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020179205.

The SARS-CoV-2 virus has caused millions of confirmed COVID-19 cases worldwide and hundreds of thousands of deaths in less than 6 months. Mitigation measures including social distancing were implemented to control disease spread, however, thousands of new cases continue to be diagnosed daily. To resume some suspended social activities, early diagnosis and contact tracing are essential. To meet this required diagnostic and screening capacity, high throughput diagnostic assays are needed. The NeuMoDx SARS-CoV-2 assay, performed on a NeuMoDx molecular system, is a rapid, fully automated, qualitative real-time RT-PCR diagnostic test with throughput of up to 288 tests in an 8-h shift. The assay received emergency use authorization from the FDA and is used in some large testing centers in the US. This paper describes the analytical and clinical performance of the assay at three centers: Johns Hopkins Hospital, St. Jude Children's Research Hospital, and the Wadsworth Center.

The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school's closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school's closure.

Italy recorded its first case of confirmed acute respiratory illness because of coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection. Despite these measures, the number of infected people is growing exponentially, with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dress code modalities, implemented in our hospital to prevent further dissemination of COVID-19 infection.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), may result in severe complications, multiorgan dysfunction, acute respiratory failure, and death. SARS-CoV-2 is highly contagious and places healthcare workers at significant risk, especially during aerosol-generating procedures, including airway management. OBJECTIVE: This narrative review outlines the underlying respiratory pathophysiology of patients with COVID-19 and discusses approaches to airway management in the emergency department (ED) based on current literature. DISCUSSION: Patients presenting with SARS-CoV-2 infection are at high risk for acute respiratory failure requiring airway management. Among hospitalized patients, 10-20% require intensive care unit admission, and 3-10% require intubation and mechanical ventilation. While providing respiratory support for these patients, proper infection control measures, including adherence to personal protective equipment policies, are necessary to prevent nosocomial transmission to healthcare workers. A structured approach to respiratory failure in these patients includes the use of exogenous oxygen via nasal cannula or non-rebreather, as well as titrated high-flow nasal cannula and non-invasive ventilation. This review offers several guiding principles and resources designed to be adapted in conjunction with local workplace policies for patients requiring respiratory support. CONCLUSIONS: While the fundamental principles of acute respiratory failure management are similar between COVID-19 and non-COVID-19 patients, there are some notable differences, including a focus on provider safety. This review provides an approach to airway management and respiratory support in the patient with COVID-19.

BACKGROUND & AIMS: Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. METHODS: We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. RESULTS: Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%). Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. CONCLUSIONS: In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.

OBJECTIVE: The COVID-19 pandemic poses an unprecedented threat to the health and economic prosperity of the world's population. Yet, because not all regions are affected equally, this research aims to understand whether the relative growth rate of the initial outbreak in early 2020 varied significantly between the US states and counties. STUDY DESIGN: Based on publicly available case data from across the USA, the initial outbreak is statistically modeled as an exponential curve. METHODS: Regional differences are visually compared using geo maps and spaghetti lines. In addition, they are statistically analyzed as an unconditional model (one-way random effects analysis of variance estimated with HLM 7.03); the bias between state- and county-level models is evidenced with distribution tests and Bland-Altman plots (using SPSS 26). RESULTS: At the state level, the outbreak rate follows a normal distribution with an average relative growth rate of 0.197 (doubling time 3.518 days). But there is a low degree of reliability between state-wide and county-specific data reported (Intraclass correlation coefficient ICC = 0.169, P < 0.001), with a bias of 0.070 (standard deviation 0.062) as shown with a Bland-Altman plot. Hence, there is a significant variation in the outbreak between the US states and counties. CONCLUSIONS: The results emphasize the need for policy makers to look at the pandemic from the smallest population subdivision possible, so that countermeasures can be implemented, and critical resources provided effectively. Further research is needed to understand the reasons for these regional differences.

On December 31, 2019, the novel human coronavirus (COVID-19) was identified in Wuhan, China and swiftly spread in all nations and territories around the globe. There is much debate about the major route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions. So, more evidence is required to determine the potential pathway of transmission of SARS-CoV-2 including airborne transmission. Therefore, we examined the potential aerosol transmission of the virus through hospital wards indoor air by confirmed COVID-19 patients on May 7, 2020. In order to capture airborne SARS-CoV-2, the liquid impinger biosampler was used to take fourteen air samples in different wards of the indoor air of the hospital. The specific primer and probe real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were applied to detect viral genomes of the SARS-CoV-2 virus in positive air samples. Accordingly, we found two positive air samples (in the ICU) out of 14 ones taken from different wards with confirmed COVID-19 patients. The results revealed the possibility of airborne transmission of SARS-CoV-2 though more studies are required to determine the role of actual mechanisms such as cough, sneeze, normal breathing and speaking in the emission of airborne size carrier aerosols. Likewise, more quantitative analyses are needed to estimate airborne viability of SARS-CoV-2 in the carrier aerosols.

The World Health Organization declared the novel coronavirus, or COVID-19, a pandemic in March 2020. Given the severity of COVID-19, appropriate use criteria have been implemented for fetal echocardiography. Screening low risk pregnancies for critical congenital heart disease has typically been a shared responsibility by pediatric cardiologists, obstetricians, and maternal fetal medicine (MFM). Currently, many of the fetal echocardiograms for low risk pregnancies for critical congenital heart disease have been deferred or cancelled with the emphasis on suspected abnormalities by MFMs and obstetricians. In this review, we discuss the literature that has been the basis of screening of low risk pregnancies by pediatric cardiologists. A new approach to more widespread usage of fetal tele-echocardiography may play a large part during COVID-19 and may continue after the pandemic.

This Preview summarizes the Ada Lovelace Institute rapid evidence review Exit through the App Store?, which sets out proposals for whether, and how, the UK government should use technology to transition from the COVID-19 global public health crisis. It examines the potential development and implementation of technical solutions to support symptom tracking, contact tracing, and immunity certification. The full rapid evidence review takes into account societal, political, legal, and ethical perspectives and gives findings and recommendations for the transition and rebuild phases that follow containment, delay, and mitigation.

In the absence of an efficient drug treatment or a vaccine, the control of the COVID-19 pandemic relies on classic infection control measures. Since these means are socially disruptive and come with substantial economic loss for societies, a better knowledge of the epidemiology of the new coronavirus epidemic is crucial to achieve control at a sustainable cost and within tolerable restrictions of civil rights.

We recently reported that inhibitors against human dihydroorotate dehydrogenase (DHODH) have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells. However, there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019 (COVID-19) patients. In the present study, we evaluated Leflunomide, an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases, in treating COVID-19 disease with a small-scale of patients. Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included. Five of the patients were treated with Leflunomide, and another five were treated as blank controls without a placebo. All the patients accepted standard supportive treatment for COVID-19. The patients given Leflunomide had a shorter viral shedding time (median of 5 days) than the controls (median of 11 days, P = 0.046). The patients given Leflunomide also showed a significant reduction in C-reactive protein levels, indicating that immunopathological inflammation was well controlled. No obvious adverse effects were observed in Leflunomide-treated patients, and they all discharged from the hospital faster than controls. This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

In December 2019, the novel COVID-19 virus spread from a cluster of pneumonia cases in Wuhan, China, to every corner of the globe, creating a worldwide pandemic pushing hospital systems past capacity and bringing economies worldwide to a halt. The COVID-19 pandemic is unique in comparison to prior coronavirus epidemics in its superior ability to be spread by asymptomatic and presymptomatic patients, allowing the virus to silently evade traditional symptoms-based screening approaches. Countries have implemented cutting-edge digital solutions to enhance traditional contact-tracing methodologies in combination with novel testing strategies to combat the virus, with variable levels of success. Despite having one of the most advanced and expensive health care systems in the world, the United States (U.S.) response is arguably one of the world's largest failures, as it leads the globe in case number as well as deaths. Until a successful vaccine can be broadly distributed, it is imperative that the U.S. curb the viral spread by rapidly developing a framework implementing both enhanced tracing and testing strategies balancing the needs of public health while respecting individual liberties. This review will explore the role of technology-augmented contact-based surveillance in tracking the outbreak in select countries in comparison to the current U.S. approach. It will evaluate barriers in the U.S. to implementing similar technologies, focusing on privacy concerns and a lack of unified testing and tracing strategy. Finally, it will explore strategies for rapidly scaling testing in a cost-effective manner.

Since the start of the COVID-19 pandemic there has been much debate in the media on whether masks should be worn to stop the spread of the virus. There are two ways in which they could work. Firstly, to protect the person wearing the mask, and secondly, to reduce the likelihood of the person wearing the mask passing the disease on to anyone else. This is not an easy issue to address and many factors come into play such as droplet size, aerosol transmission and the viral load, as well as the specific properties of any given mask. The method used in this study was to measure the change in relative humidity when wearing a mask, compared to no mask, in various scenarios, based on the assumption that as the virus is air-borne the smaller the increase in humidity the less the spread of the virus. The results above show that the use of a mask, excluding some simple home-made ones, significantly reduces the spread of humidity. However, their effectiveness is device specific and needs to be considered in greater detail for each type of mask, especially the direction of escaping air when forward flow is blocked.

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.

This prospective observational cohort study is based on the first 500 patients who requested emergency teleconsultation during the initial days of the COVID-19 lockdown in Paris, France between 20 March and 10 April 2020. It is the first study to assess the utility of emergency teleophthalmology with a simple smartphone application or web browser and a webcam to manage emergency eye care in a population with sudden restricted access to ophthalmologists. In this study, every patient who asked for an ophthalmic emergency consultation in a single specialized center in Paris ('SOS OEil') first had to undergo a teleconsultation appointment to evaluate the indication for a physical consultation to preserve lockdown. Under medical advice only, a physical appointment was given within a day (if necessary). The aim of the study was to describe the population and diagnoses and evaluate the main judgment criteria, defined as the 'ability of teleconsultation to properly indicate a physical consultation for fair diagnosis and treatment in eye emergencies'. This organization has permitted physicians and patients to preserve social distancing while avoiding 3 or 4 physical consultations per person. Notably, 27% of teleconsultations were followed by a physical appointment. There was a mean 4.12-day delay between symptom apparition and consultation, and less than 1 day for traumas, superficial corneal foreign body and neuro-ophthalmological emergencies. There was a 96% sensitivity and 95% specificity to properly evaluate the indication of a physical consultation and only 1.0% misdiagnoses that lead to delayed care. Hence, teleconsultation maintained satisfactory healthcare access to patients with severe ophthalmological disorders while preserving social distancing and sanitary precautions. Therefore, teleconsultation may be seriously considered as a way to efficiently regulate ophthalmic emergencies, especially for patients with limited access to a specialist.

Background: India has reported more than 70,000 cases and 2000 deaths. Pune is the second city in the Maharashtra state after Mumbai to breach the 1000 cases. Total deaths reported from Pune were 158 with a mortality of 5.7%. To plan health services, it is important to learn lessons from early stage of the outbreak on course of the disease in a hospital setting. Objectives: To describe the epidemiological characteristics of the outbreak of COVID-19 in India from a tertiary care hospital. Methods: This was a hospital-based cross-sectional study which included all admitted laboratory confirmed COVID19 cases from March 31, to April 24, 2020. The information was collected in a predesigned pro forma which included sociodemographic data, duration of stay, family background, outcome, etc., by trained staff after ethics approval. Epi Info7 was used for data analysis. Results: Out of the total 197 cases, majority cases were between the ages of 31-60 years with slight male preponderance. Majority of these cases were from the slums. Breathlessness was the main presenting symptom followed by fever and cough. More than 1/5(th) of patients were asymptomatic from exposure to admission. The case fatality rate among the admitted cases was 29.4%. Comorbidity was one of the significant risk factors for the progression of disease and death (odds ratio [OR] = 16.8, 95% confidence interval [CI] = 7.0 - 40.1, P < 0.0001). Conclusion: Mortality was higher than the national average of 3.2%; comorbidity was associated with bad prognosis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

OBJECTIVES: Explore how to manage oral healthcare during the COVID-19 outbreak. MATERIALS AND METHODS: In order to solve oral healthcare during the COVID-19 outbreak, our hospital has taken effective measures: build a team of experts, which provide a 24-h hotline, online video consultation, and online training and push popular science articles on WeChat. For the treatment of emergency patients aside from routine epidemic prevention measures, some special measures for oral treatment need to be added. RESULTS: From January 23, 2020, to March 2, 2020, a total of 3035 patients received oral therapy during the COVID-19 epidemic in our hospital. To our knowledge, no oral health worker or patient has been infected with COVID-19 due to oral treatment, and no patients have complained about the suspension of treatment by complaints hotline. CONCLUSION: COVID-19 is a novel challenge for oral healthcare. Attention should be paid to oral healthcare during the outbreak of COVID-19. CLINICAL RELEVANCE: These experiences of oral healthcare can be used as a reference by stomatological hospitals and oral clinics during public health emergencies.

In this viewpoint, we summarize the relevance of thromboinflammation in COVID-19 and discuss potential mechanisms of endothelial injury as a key point for the development of lung and distant organ dysfunction, with a focus on direct viral infection and cytokine-mediated injury. Entanglement between inflammation and coagulation and resistance to heparin provide a rationale to consider other therapeutic approaches in order to preserve endothelial function and limit microthrombosis, especially in severe forms. These strategies include nebulized heparin, N-acetylcysteine, plasma exchange and/or fresh frozen plasma, plasma derivatives to increase the level of endogenous anticoagulants (tissue factor pathway inhibitor, activated protein C, thrombomodulin, antithrombin), dipyridamole, complement blockers, different types of stem cells, and extracellular vesicles. An integrated therapy including these drugs has the potential to improve outcomes in COVID-19.

A novel human coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic of coronavirus disease 2019 (COVID-19). In this study, we aimed to explore the clinical characteristics and outcomes in older patients with COVID-19. Ninety-one patients with SARS-CoV-2 infection were included in the study, 27 of which (29.67%) were elderly. The median age of these 27 patients was 74.9 years (interquartile range 68-82; range 65-94 years), and 15 (55.56%) were female. Elderly with COVID-19 in Beijing (China) were more likely to have underlying comorbidities and more frequently tended to have critical illness and suffer from more complications. The main treatments of the elderly consisted of symptomatic and respiratory support. The most frequent complications in the elderly were pleural effusion [10, (37.04%)], secondary infection [7, (25.93%)], and kidney damage [7, (25.93%)]. Six (22.22%) of the 27 elderly patients received invasive ventilation (three of them switched to extracorporeal membrane oxygenation). As of March 7, 20 (74.07%) of the 27 elderly patients were discharged, two (7.41%) were still hospitalized, and five died; the mortality in the elderly was 18.52%. Age was associated with the mortality in patients with COVID-19 (OR 0.82; 95% CI 0.70-0.97; P = 0.019). Therefore, more attention should be paid to the treatment of comorbidities and complications in elderly patients.

OBJECTIVE: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses. METHODS: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with OS and pathologic stage. RESULTS: We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with Charlson Comorbidity Index = 0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, P= .002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, P = 309). Pathologic stage (pT or pN) was not associated with surgical delay. CONCLUSION: Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay versus the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves of the COVID-19 pandemic.

BACKGROUND: The recent COVID-19 pandemic has accelerated the treatment process through IT/technological supports, useful in the management of chronic patients such as those affected by type 1 Diabetes Mellitus (T1DM). Specific routes for fragile patients such as those with micro-infusers have been created thanks to the application of "Diabetes Technology," which allows patients to monitor blood glucose quickly and easily. The present pilot study aimed to assess the quality of care provided to patients with micro-infusers in a delicate phase such as a pandemic lockdown. MATERIALS AND METHODS: A mixed-methods approach was used. In the first part, with prior written consent, patients with insulin pumps enrolled voluntarily. In the second part, the focus group discussion (FGD) was carried out with the voluntarily enrolled participants. The FGD data were organized and analyzed by the thematic areas. RESULTS: The number of patients with afferent insulin pumps at the center was 50 individuals. Among them, 20 patients voluntarily joined the first part of the study by completing the PACIC questionnaire, which gave an average result of 3.34 (min. 2.2 and max. 4.2). In the second part, the application of the focus group technique demonstrated that technology is decisive in the management of diabetic pathology, not only in the emergency phase. CONCLUSIONS: At the time of public health crises, alternative strategies such as Tele-Nursing or Telemedicine could be crucial for the management of patients with micro-infuser not only in critical moments, such as lockdown, but also in ordinary health management.

BACKGROUND: Milder symptoms were observed in children with COVID-19. However, whether this also holds true for neonates is not known. METHODS: The clinical data of a total of 3213 patients aged 2 years or below, including 749 neonates, in Brazil nationwide were studied. Comparisons were made between neonate and infant patients by conducting statistical tests. RESULTS: Neonates appeared to bear more severe clinical courses. In addition to higher case fatality rates, newborns with COVID-19 had much shorter time from symptom onset to death and longer time from symptom onset to discharge. Dyspnoea, sore throat and cough were more prominent in neonate patients, suggestive of both upper and lower respiratory tract infection, as opposed to upper respiratory tract symptoms mostly observed in children. CONCLUSION: Findings suggested that trained immunity provides a possible explanation because the innate immune system in newborns is not "well-trained" while that in adult tends to hyperactive.

Background: Patients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease 2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality. Methods: This retrospective multicentric cohort study used the Programme de Medicalisation des Systemes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts. Findings: Eighty-nine patients were included. The median age was 67 years (range, 19-92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62-81%). In multivariable analysis, having an age >/= 70 years (hazard ratio 2.87, 1.20-6.85, p = 0.02) and relapsed/refractory lymphoma (hazard ratio 2.54, 1.14-5.66, p = 0.02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3.20, 1.33-7.72, p = 0.01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%). Interpretation: Thirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population. Funding: There have been no specific funds to run this study.

As corona virus disease 2019 (COVID-19) is a rapidly growing public health crisis across the world, our knowledge of meaningful diagnostic tests and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still evolving. This novel coronavirus disease COVID-19 can be diagnosed using RT-PCR, but inadequate access to reagents, equipment, and a nonspecific target has slowed disease detection and management. Precision medicine, individualized patient care, requires suitable diagnostics approaches to tackle the challenging aspects of viral outbreaks where many tests are needed in a rapid and deployable approach. Mass spectrometry (MS)-based technologies such as proteomics, glycomics, lipidomics, and metabolomics have been applied in disease outbreaks for identification of infectious disease agents such as virus and bacteria and the molecular phenomena associated with pathogenesis. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is widely used in clinical diagnostics in the United States and Europe for bacterial pathogen identification. Paper spray ionization mass spectrometry (PSI-MS), a rapid ambient MS technique, has recently open a new opportunity for future clinical investigation to diagnose pathogens. Ultra-high-pressure liquid chromatography coupled high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics have been employed in large-scale biomedical research to discriminate infectious pathogens and uncover biomarkers associated with pathogenesis. PCR-MS has emerged as a new technology with the capability to directly identify known pathogens from the clinical specimens and the potential to identify genetic evidence of undiscovered pathogens. Moreover, miniaturized MS offers possible applications with relatively fast, highly sensitive, and potentially portable ways to analyze for viral compounds. However, beneficial aspects of these rapidly growing MS technologies in pandemics like COVID-19 outbreaks has been limited. Hence, this perspective gives a brief of the existing knowledge, current challenges, and opportunities for MS-based techniques as a promising avenue in studying emerging pathogen outbreaks such as COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However, the information of COVID-19 and influenza coinfection is limited. In this study, we reported our coinfected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19-influenza differentiation. During the study period, 1103 patients have been diagnosed with COVID-19. Among them, six patients (0.54%) were diagnosed coinfected with influenza. There have been 28 more coinfected patients reported. Laboratory-based screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in five and with influenza in one of our patients. Our cases were mild to moderate in severity. The reported cases in the literature included patients died (n = 2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza coinfection is rare. Screening studies report more cases, suggesting that unless screening patients with COVID-19, the coinfection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work.

Deep learning is an important branch of artificial intelligence that has been successfully applied into medicine and two-dimensional ligand design. The three-dimensional (3D) ligand generation in the 3D pocket of protein target is an interesting and challenging issue for drug design by deep learning. Here, the MolAICal software is introduced to supply a way for generating 3D drugs in the 3D pocket of protein targets by combining with merits of deep learning model and classical algorithm. The MolAICal software mainly contains two modules for 3D drug design. In the first module of MolAICal, it employs the genetic algorithm, deep learning model trained by FDA-approved drug fragments and Vinardo score fitting on the basis of PDBbind database for drug design. In the second module, it uses deep learning generative model trained by drug-like molecules of ZINC database and molecular docking invoked by Autodock Vina automatically. Besides, the Lipinski's rule of five, Pan-assay interference compounds (PAINS), synthetic accessibility (SA) and other user-defined rules are introduced for filtering out unwanted ligands in MolAICal. To show the drug design modules of MolAICal, the membrane protein glucagon receptor and non-membrane protein SARS-CoV-2 main protease are chosen as the investigative drug targets. The results show MolAICal can generate the various and novel ligands with good binding scores and appropriate XLOGP values. We believe that MolAICal can use the advantages of deep learning model and classical programming for designing 3D drugs in protein pocket. MolAICal is freely for any nonprofit purpose and accessible at https://molaical.github.io.

A 66-year-old male patient with coronavirus disease-19 (COVID-19) developed cardiogenic shock with echocardiographic evidence of decreased left ventricular ejection fraction and global hypokinesia concomitant with a robust systemic inflammatory response. Following the administration of convalescent plasma therapy and inotropic support, left ventricular function recovered fully in accordance with the decrease in the concentration of the inflammatory markers. Thus, we demonstrate the presence of transient reversible cardiomyopathy in a patient with severe COVID-19 and illustrate the association of acute cardiac dysfunction with profound systemic inflammation among COVID-19 patients.

Evidence of neurological complications and direct affection of neuronal structures in the course of infections with SARS-CoV-2 is actually emerging. Therefore adequate medical care for neurological patients must also be guaranteed as part of the current SARS-CoV-2 pandemic. Multiple, peripheral and central neurological affections have been described, such as particular headache, consciousness disorders, cranial nerve disorders, peripheral nerve damage, epileptic seizures and ischemic events. Since abundant information on COVID-19 is published on a daily basis, this article aims to summarize and evaluate the current literature on this topic.

The COVID-19 pandemic presented an unprecedented opportunity to test the emergency management plan of one large urban teaching hospital. In this article, a detailed description of the hospital's surge planning process with lessons learned has been provided.

The corona virus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel corona virus SARS-CoV2, previously named as 2019-nCoV. COVID-19 has spread across the globe and declared as pandemic by World health organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, so repurposing of existing drugs is the only solution. Novel drug delivery systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for treatment of various viral diseases and their relevance in COVID-19 has discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for a potential targeted delivery. So in these tough times, NDDS and nanotechnology can be a safeguard to humanity.

BACKGROUNDSerological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals.METHODSWe studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010-2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients.RESULTSAntibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival.CONCLUSIONThe measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.TRIAL REGISTRATIONCOVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDINGIRCCS Ospedale San Raffaele and Universita Vita Salute San Raffaele.

The new coronavirus SARS-CoV-2 virus is causing a severe pneumonia in human, provoking the serious outbreak epidemic CoV-2. Since its appearance in Wuhan, China on December 2019, CoV-2 becomes the biggest challenge the world is facing today, including the discovery of antiviral drug for SARS-CoV-2. In this study, the potential inhibitory of a class of human SARS inhibitors, namely pyridine N-oxide derivatives, against CoV-2 was addressed by quantitative structure-activity relationship 3 D-QSAR. The reliable CoMSIA developed model of 110 pyridine N-oxide based-antiviral compounds, showed Q(2)= 0.54 and[Formula: see text] The molecular surflex-docking was applied to identify the crystal structure of CoV-2 main protease 3CLpro (PDB: 6LU7) and two potentially and largely used antiviral molecules, namely chloroquine, hydroxychloroquine. The obtained free energy affinity and ADMET properties indicate that among the series of model antiviral compounds examined, the new antiviral compound A5 could be an excellent antiviral drug inhibitor against COVID-19. The inhibition activity of pyridine N-oxyde compounds against CoV-2 was compared with the activity of two common antiviral drug, namely chloroquine (CQ) and hydroxychloroquine (HCQ). DFT method was also used to define the sites of reactivity of pyridine N-oxyde derivatives as well as CQ and HCQ. Communicated by Ramaswamy H. Sarma.

A novel coronavirus infection, which began as an outbreak of unusual viral pneumonia in Wuhan, a central city in China, has evolved into a global health crisis. The outbreak is an unembellished reminder of the hazard coronaviruses pose to public health. Government and researchers around the world have been taking swift measures to control the outbreak and conduct aetiological studies to understand the various facets of the outbreak. This review is an attempt at providing an insight about the current understanding, knowledge gaps and a perspective on the future of coronavirus disease 2019 (COVID-19) infections. All the authentic data published so far on COVID-19 has been systematically analysed. PubMed, NCBI, World Health Organisation, Ministry of Health and Family Welfare (India), and Centers for Disease Control and Prevention databases and bibliographies of relevant studies up to 22(nd) June 2020 have been included. The Wuhan outbreak is a stark reminder of the continuing threat posed by zoonotic diseases to global health. Despite an armamentarium of Government officials, researchers and medical fraternity working towards the containment of this novel coronavirus viral pneumonia continues to spread at an alarming rate infecting multitudes and claiming hundreds of lives.

The year of 2020 teaches us to prevent is always better than to cure. It is an old phrase that is being used for decades, but it is never been implemented cordially by our society nowadays. Covid-19 is a good lesson that reminds us to carefully prevent the spread of coronavirus which is now a pandemic worldwide. People now wash their hands more often and clean, wear a mask everywhere - everytime, do physical distancing, do healthy lifestyle such as physical activity, healthy diet, and consume multivitamins. They obey the cough and sneeze etiquette. Prevention awareness is never been such popular like todays.For internal medicine specialist, the role for prevention is very broad. Besides we still have a role in primary prevention, we can take our part in both secondary and (of course) tertiary prevention. Primary prevention can be defined as an action not allow a disease to occur, for examples vaccination (for internal medicine specialist more specific as adult vaccination), smoking cessation, physical activity (exercise) and healthy diet. Health promotion and prevention is the core of primary prevention. Secondary prevention aims to detect the disease as early as possible, in at risk population, such as mammography for breast cancer, swab test for Covid-19, colonoscopy for colon cancer in high risk patients. Last, tertiary prevention propose to hamper the progress of clinical disease and prevent more severe complications of the disease, for examples cardiac rehabilitation, or medications for prevent chronic kidney disease in patients with diabetes or hypertension. It is overlapping the curative or treatment strategies as it is states "to cure is to prevent". In 2020, in which each underlying conditions require effective treatment and each disease should be prevented. We are now facing the era of preventive medicine. As an internal medicine specialist, we need to put in mind a philosophy of prevention in every of our action towards patient's care and services.

BACKGROUND: This study was intended to investigate the epidemiological characteristics of COVID-19 clusters and the severity distribution of clinical symptoms of involved cases in Sichuan Province, so as to provide information support for the development and adjustment of strategies for the prevention and control of local clusters. METHODS: The epidemiological characteristics of 67 local clusters of COVID-19 cases in Sichuan Province reported as of March 17, 2020 were described and analyzed. Information about all COVID-19 clusters and involved cases was acquired from the China Information System for Disease Control and Prevention and analyzed with the epidemiological investigation results taken into account. RESULTS: The clusters were temporally and regionally concentrated. Clusters caused by imported cases from other provinces accounted for 73.13%; familial clusters accounted for 68.66%; the average attack rate was 8.54%, and the average secondary attack rate was 6.11%; the median incubation period was 8.5 d; a total of 28 cases met the criteria for incubation period determination, and in the 28 cases, the incubation period was > 14 d in 21.43% (6/28). a total of 226 confirmed cases were reported in the 67 clusters. Ten cases were exposed before the confirmed cases they contacted with developed clinical symptoms, and the possibility of exposure to other infection sources was ruled out; two clusters were caused by asymptomatic carriers; confirmed cases mainly presented with fever, respiratory and systemic symptoms; a gradual decline in the severity of clinical symptoms was noted with the increase of the case generation. CONCLUSIONS: Population movement and gathering restrictions and strict close contact management measures will significantly contribute to the identification and control of cases. Transmission during the incubation period and asymptomatic infections have been noted. Studies on the pathogenicity and transmissibility in these populations and on COVID-19 antibody levels and protective effects in healthy people and cases are required.

BACKGROUND: In an effort to contain the effects of the coronavirus disease (COVID-19) pandemic, health care systems worldwide implemented telemedical solutions to overcome staffing, technical, and infrastructural limitations. In Germany, a multitude of telemedical systems are already being used, while new approaches are rapidly being developed in response to the crisis. However, the extent of the current implementation within different health care settings, the user's acceptance and perception, as well as the hindering technical and regulatory obstacles remain unclear. OBJECTIVE: The aim of this paper is to assess the current status quo of the availability and routine use of telemedical solutions, user acceptance, and the subjectively perceived burdens on telemedical approaches. Furthermore, we seek to assess the perception of public information quality among professional groups and their preferred communication channels. METHODS: A national online survey was conducted on 14 consecutive days in March and April 2020, and distributed to doctors, nurses, and other medical professionals in the German language. RESULTS: A total of 2827 medical professionals participated in the study. Doctors accounted for 65.6% (n=1855) of the professionals, 29.5% (n=833) were nursing staff, and 4.9% (n=139) were identified as others such as therapeutic staff. A majority of participants rated the significance of telemedicine within the crisis as high (1065/2730, 39%) or neutral (n=720, 26.4%); however, there were significant differences between doctors and nurses (P=.01) as well as between the stationary sector compared to the ambulatory sector (P<.001). Telemedicine was already in routine use for 19.6% (532/2711) of German health care providers and in partial use for 40.2% (n=1090). Participants working in private practices (239/594, 40.2%) or private clinics (23/59, 39.0%) experienced less regulatory or technical obstacles compared to university hospitals (586/1190, 49.2%). A majority of doctors rated the public information quality on COVID-19 as good (942/1855, 50.8%) or very good (213/1855, 11.5%); nurses rated the quality of public information significantly lower (P<.001). Participant's age negatively correlated with the perception of telemedicine's significance (rho=-0.23; P<.001). CONCLUSIONS: Telemedicine has a broad acceptance among German medical professionals. However, to establish telemedical structures within routine care, technical and regulatory burdens must be overcome.

Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a self-limited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4(+) T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-alpha, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARS-CoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1beta seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8(+) T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology.

The world is currently face to face with a pandemic which is spreading rapidly across the globe caused by SARS-CoV-2, a strain of Coronaviruses (CoVs) belonging to subgenus Sarbecovirus of genus Betacoronavirus. World Health Organisation (WHO) on 11 Feb 20 named this disease caused by SARS-CoV-2 as Covid-19. This pandemic is spreading rapidly and more than 20,00,000 cases have occurred globally. The human Coronaviruses discovered in 1960s were considered potentially harmless endemic viruses with seasonal distribution before late 2002. The CoVs are found in a large number of domestic and wild animals and birds. The first pandemic caused by Coronavirus caused by SARS-CoV was recognized in the late 2002 in Guangdong Province and resulted in widespread morbidity and mortality. This was followed by MERS-CoV which began in 2012 in the Arabian peninsula with multiple outbreaks related to it in various parts of the globe. Various studies have suggested how these viruses made their entry from their natural reservoir bats via intermediate host like civets and camels in case of SARS-CoV and MERS-CoV respectively. The intermediate host of the SARS-CoV-2 still needs to be established. The SARS-CoV-2 has 96.2% similarity to the bat Severe Acute Respiratory Syndrome related-Coronavirus (SARSr-CoV RaTG13). SARS-CoV-2 has been found to be more distant in relation to SARS-CoV (79%) and MERS-CoV (50%). At the whole genome sequence level pangolin CoV and SARSr-CoV RaTG13 show 91.02% and 96.2% similarity with SARS-CoV-2 but the S1 subunit of spike protein of pangolin CoV is more closely related to SARS-CoV-2 than SARSr-CoV RaTG13. The genetic analysis of the currently circulating strains of the pandemic have shown 99.98-100% similarity in their genomes implying a recent shift to humans. The animal source of SARS-CoV-2 needs to be identified to implement control measures in the present pandemic. Also, how the virus moves interspecies will help predict and prevent future pandemics.

Background: This descriptive, unplanned investigation has been undertaken to report reactions, attitudes and countermeasures which have been put in place and implemented by medical oncology units facing the COVID-19 outbreak in Southern Italy. Materials and methods: Data have been retrospectively obtained from the time-related analysis of conversations via a WhatsApp messenger-based group chat between the medical directors belonging to the Italian College of Medical Oncology Directors. Overall number, intensity and time trend of conversations related to reactions during the 4 weeks of observation related to the crucial events which occurred between 24 February and 28 March, 2020 2020 are included. A sentiment analysis of conversations was also carried out. Results: We report 956 conversations among 19 medical oncology units related to reactions to the crucial events, such as epidemic spread, Government ordinances and guidelines during the 4 weeks of observation. Data show significant awareness of problems linked to the COVID-19 spread among oncologists and rapid diffusion of countermeasures. Actions taken were correlated time wise to crucial events. A correlation between conversations and the volume of activity of oncology units was found. By analysing the sentiment analysis of raw data, positive emotions were reduced in percentage over the weeks. A significant increase in negative emotions was observed as the outbreak impacted on the healthcare system. Conclusion: In our experience, the WhatsApp instant-messaging system seems to be a useful tool to share news and reactions between medical oncologists to rapidly implement necessary health measures and answers to most cancer patients' needs and queries in the COVID-19 pandemic scenario.

PURPOSE: To investigate the effectiveness of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS), which occur as a natural result of aging and androgen exposure, in predicting disease prognosis in male patients diagnosed with COVID-19. METHODS: The study was planned prospectively. The study included 63 male patients over 40 years of age diagnosed with COVID-19. The patients were diagnosed with COVID-19 based on the results of reverse transcription polymerase chain reaction tests of oropharyngeal and nasopharyngeal swabs obtained as per the World Health Organization guidelines. The presence of LUTS was assessed by the International Prostate Symptom Score (I-PSS), a subjective assessment, and the I-PSS was filled for the patients included in the study. The patients were divided into three groups based on their scores in the I-PSS survey: group 1: mild (0-7), group 2: moderate (8-19), and group 3: severe (20-35). The data of all three groups were statistically analyzed. RESULTS: In the assessment performed between the groups, it was identified that for patients in group 3, the length of hospital stay was longer, intensive care requirement was more frequent, and their mortality rates were numerically higher. In the evaluation made regarding the time to intensive care admittance, this was identified to be the shortest in group 3. CONCLUSION: As a result of our study, we think that in patients with COVID-19, BPH-related LUTS can guide clinicians in predicting prognosis.

COVID 19 pandemic has affected the delivery of surgical services as a part of management of head and neck cancers all over the world. Since it may affect the overall cure as well as quality of life of these patients, it is necessary to continue providing surgical treatment but with minimal additional health hazards to the patient or the health care worker. For this, a workflow was formulated in a university teaching hospital in India with large head and neck cancer workload and implemented during the period of national lockdown. 125 major head and neck cancer cases were operated during this period out of which 25 patients were of high-risk status. Emergency (10%) and semi-emergency (83%) cases predominated with few electives. The number of noncancer reconstructive and craniomaxillofacial cases operated was 81, out of which 25% was of emergency in nature. When compared to the data of similar period in the previous year, 60% of the workload in the cancer-related cases could be offered surgical treatment, whereas the noncancer cases operated were only 25%. The workflow may be useful for all surgical departments in safely performing procedures during this pandemic or similar situations in future with suitable refinements.

Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently emerged as a global health threat. To address this health emergency, various therapeutic approaches are currently under investigation. There is limited evidence on the effectiveness of hydroxychloroquine (HCQ) and chloroquine (CQ) as COVID-19 therapies, and thus World Health Organization (WHO) mentioned that "Current data shows that this drug does not reduce deaths among hospitalized COVID-19 patients, nor help people with mild or moderate disease." CQ and HCQ are typically used for the treatment of malaria but have been recognized for certain beneficial effects in COVID-19 patients based on some clinical outcomes from the clinical treatment of COVID-19. A standard dose of HCQ has been proven effective and less toxic than CQ in COVID-19 patients; however, a comprehensive understanding of a patient's clinical condition is necessary. Based on several hospital findings, the Food and Drug Administration (FDA) has officially cancelled the emergency use authorization for HCQ and CQ for treating hospitalized COVID-19 patients on June 15, 2020. In this review, we highlight both pros and cons of the clinical use of CQ and HCQ in COVID-19 patients.

Pending the availability of vaccines to contain the SARS-CoV-2 pandemic, the current solution is "social distancing" with a reduction of dental treatments to those assessed as urgent and emergency cases. These treatments also involve Early Childhood Caries (ECC) due to the fact that this disease affects preschool children (a vulnerable population) and, in addition, shows a propensity to evolve into more serious complications (dental pain, infections). A narrative review was carried out to support a protocol for treating ECC with efficacious and safe (in terms of SARS-CoV-2 transmission) procedures. Protocol involves criteria for patients' selection remotely (telemedicine), and well-detailed criteria/equipment and hygiene procedures to combat against SARS-CoV-2 transmission. Moreover, the protocol proposes innovative caries treatments, named Minimally Invasive Treatments (MITs), well known in pedodontics for their high level of children's acceptance during dental care. MITs allow for caries removal (particularly in primary teeth) without any high-speed rotating instrument cooled with nebulized air-water spray (with high risk of virus environmental diffusion), usually adopted during traditional treatments. For evaluating MITs effectiveness in caries management, only Systematic Review and Randomized Controlled Trials (RCTs) were included in our study, without any risk of bias assessment. The indications proposed in this protocol could support clinicians for the temporary management of ECC until the SARS-CoV-2 pandemic ends.

In December 2019, a novel coronavirus was isolated from the respiratory epithelium of patients with unexplained pneumonia in Wuhan, China. This pathogen, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a pathogenic condition that has been termed coronavirus disease 2019 (COVID-19) and has reached pandemic proportions. As of 17 September 2020, more than 30 million confirmed SARS-CoV-2 infections have been reported in 204 different countries, claiming more than 1 million lives worldwide. Accumulating evidence suggests that SARS-CoV-2 infection can lead to a variety of clinical conditions, ranging from asymptomatic to life-threatening cases. In the early stages of the disease, most patients experience mild clinical symptoms, including a high fever and dry cough. However, 20% of patients rapidly progress to severe illness characterized by atypical interstitial bilateral pneumonia, acute respiratory distress syndrome and multiorgan dysfunction. Almost 10% of these critically ill patients subsequently die. Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response - characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy - in disease exacerbation. These insights may aid the identification of new or existing therapeutic interventions to limit the progression of early disease and treat severe cases.

OBJECTIVE: Patients with cancer are usually immunosuppressive and susceptible to COVID-19 infection. Asymptomatic COVID-19 cases are infective and cannot be identified by symptom-based screening. There is an urgent need to control virus spread by asymptomatic carriers at cancer centres. We aim to describe the characteristics, screening methods, and outcomes of cancer patients with asymptomatic COVID-19 infection and to further explore anti-tumour treatment for this population. PATIENTS AND METHODS: We reviewed patients with cancer who were admitted to Hubei Cancer Hospital in Wuhan from February 1, 2020, to April 4, 2020. We collected demographic data, laboratory findings, treatment information, nucleic acid and serum test results, chest computed tomography (CT) information and survival status of cancer patients diagnosed with asymptomatic COVID-19 infection. RESULTS: A total of 16 cancer patients with asymptomatic COVID-19 infection were confirmed. The most common cancer type was breast cancer. The blood cell counts of most patients were in the normal range. Lymphocytes of 100% of asymptomatic carriers were in the normal range. Thirteen (81.3%) patients were positive for virus-specific IgM antibodies, and three (18.8%) were positive by PCR; only one (6.3%) patient showed novel coronavirus pneumonia features on CT. Three (18.3%) patients died, and the cause of death was considered malignancy caused by delaying anti-tumour treatment. CONCLUSIONS: Our study shows that the lymphocytes of 100% of asymptomatic carriers were in the normal range. This result indicates that the host immunity of asymptomatic carriers is not significantly disrupted by COVID-19. Single PCR detection is not sufficient to screen among asymptomatic individuals, and a combination of PCR tests, serological tests and CT is of great importance. Unless the tumour is life-threatening or rapidly progressing, we advise restarting active anti-tumour therapy after PCR tests become negative.

Coronavirus diseases 2019 (COVID-19) has become a worldwide pandemic affecting people at high risk and particularly at advanced age, cardiovascular and pulmonary disease. As cardiovascular patients are at high risk but also have dyspnea and fatigue as leading symptoms, prevention, diagnostics and treatment in these patients are important to provide adequate care for those with or without COVID-19 but most importantly when comorbid cardiovascular conditions are present. Severe COVID-19 with acute respiratory distress (ARDS) is challenging as patients with elevated myocardial markers such as troponin are at enhanced high risk for fatal outcomes. As angiotensin-converting enzyme 2 (ACE2) is regarded as the viral receptor for cell entry and as the Coronavirus is downregulating this enzyme, which provides cardiovascular and pulmonary protection, there is ongoing discussions on whether treatment with cardiovascular drugs, which upregulate the viral receptor ACE2 should be modified. As most of the COVID-19 patients have cardiovascular comorbidities like hypertension, diabetes, coronary artery disease and heart failure, which imposes a high risk on these patients, cardiovascular therapy should not be modified or even withdrawn. As cardiac injury is a common feature of COVID-19 associated ARDS and is linked with poor outcomes, swift diagnostic management and specialist care of cardiovascular patients in the area of COVID-19 is of particular importance and deserves special attention.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Bulk of research on this virus are carried out to unveil its multivariate pathology. Surprisingly, men are reportedly more vulnerable to COVID-19 even with higher fatality rate compared to women. Thus, it is crucial to determine whether SARS-CoV-2 infection can even affect male fertility as an immediate or long-term consequence of the disease. Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19. In contrary, hypogonadism has also been reported in the acute phase of some COVID-19 cases. Moreover, SARS-CoV-2 infection-induced uncontrolled inflammatory responses may lead to systemic oxidative stress (OS), whose severe disruptive effects on testicular functions are well-documented. This article aims to precisely present the possible impact of COVID-19 on male reproductive functions, and to highlight the speculations that need in-depth research for the exact underlying mechanisms how COVID-19 is associated with men's health and fertility.

The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern. It is imperative to identify these patients early. We show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission. We develop this model using a cohort of 1590 patients from 575 medical centers, with internal validation performance of concordance index 0.894 We further validate the model on three separate cohorts from Wuhan, Hubei and Guangdong provinces consisting of 1393 patients with concordance indexes of 0.890, 0.852 and 0.967 respectively. This model is used to create an online calculation tool designed for patient triage at admission to identify patients at risk of severe illness, ensuring that patients at greatest risk of severe illness receive appropriate care as early as possible and allow for effective allocation of health resources.

Objective: To discuss the referral mechanisms established for safe and expeditious inter-facility transfer of COVID 19 positive patients to ensure their referrals through establishing proper communication channels. Methods: Mobile phone and WhatsApp based groups, administrated by The Indus Hospital were established in April 2020. Through detailed reports and frequent communication, factors like bed and ventilator availability across these facilities are shared. Weekly reports through zoom meetings updating the key stake holders, discussion of problems faced and planning for the week ahead are also done. Result: The establishment of these groups has been successful in ensuring referral to and from The Indus Hospital to various healthcare facilities across Karachi using appropriate ambulance services. Conclusion: The development of referral mechanisms is the need of the day that has been highlighted through the COVID 19 pandemic. It is our hope that these mechanisms are sustained after the pandemic and result in improvement in patient outcome through proper referrals.

Since March 2020, Spain (along with many other countries) has been severely affected by the ongoing coronavirus disease 19 (COVID-19) pandemic caused by the rapid spread of a new virus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). As part of global efforts to improve disease surveillance, we investigated how readily SARS-CoV-2 RNA could be detected in environmental samples collected from an isolated rural community in Spain with a high COVID-19 prevalence (6% of the population of 883 inhabitants). The first diagnosis of COVID-19-compatible symptoms in the village was recorded on 3 March 2020, and the last known active case resolved on 5 June 2020. By 15 May, two months after strict movement constraints were imposed ('lockdown'), and the cumulative number of symptomatic cases had increased to 53. Of those cases, 22 (41%) had been tested and confirmed by RT-PCR. On 13 May and 5 June, samples were collected from high-use surfaces and clothes in the homes of 13 confirmed cases, from surfaces in nine public service sites (e.g. supermarket and petrol station) and from the wastewater of the village sewage system. SARS-CoV-2 RNA was detected in 7 of 57 (12%) samples, including three households and three public sites. While there is not yet sufficient evidence to recommend environmental surveillance as a standard approach for COVID-19 epidemiology, environmental surveillance research may contribute to advance knowledge about COVID-19 by further elucidating virus shedding dynamics and environmental contamination, including the potential identification of animal reservoirs.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Recently, it was confirmed that ACE2 is the receptor of SARS-CoV-2, the pathogen causing the recent outbreak of severe pneumonia around the world. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. Therefore, we hypothesized that there could be some other genes playing key roles in the entry of SARS-CoV-2 into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of SARS-CoV-2 than ACE2 (energy: -8.2 vs. -5.1 [kcal/mol]). A number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted. Finally, we suggest that AGTR2 could be a putative novel gene for the the entry of SARS-CoV-2 into human cells, which could provide different insight for the research of SARS-COV-2 proteins with their receptors.

The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities.Communicated by Ramaswamy H. Sarma.

As the world endures the coronavirus disease 2019 (COVID-19) pandemic, the conditions of 35 million vulnerable individuals struggling with substance use disorders (SUDs) worldwide have not received sufficient attention for their special health and medical needs. Many of these individuals are complicated by underlying health conditions, such as cardiovascular and lung diseases and undermined immune systems. During the pandemic, access to the healthcare systems and support groups is greatly diminished. Current research on COVID-19 has not addressed the unique challenges facing individuals with SUDs, including the heightened vulnerability and susceptibility to the disease. In this systematic review, we will discuss the pathogenesis and pathology of COVID-19, and highlight potential risk factors and complications to these individuals. We will also provide insights and considerations for COVID-19 treatment and prevention in patients with SUDs.

BACKGROUND: The SARS-CoV-2 pandemic compounds Mexico's pre-existing challenges: very high levels of both non-communicable diseases (NCD) and social inequity. METHODS AND FINDINGS: Using data from national reporting of SARS-CoV-2 tested individuals, we estimated odds of hospitalization, intubation, and death based on pre-existing non-communicable diseases and socioeconomic indicators. We found that obesity, diabetes, and hypertension are positively associated with the three outcomes in a synergistic manner. The municipal poverty level is also positively associated with hospitalization and death. CONCLUSIONS: Mexico's response to COVID-19 is complicated by a synergistic double challenge: raging NCDs and extreme social inequity. The response to the current pandemic must take both into account both to be effective and to ensure that the burden of COVID-19 not falls disproportionately on those who are already disadvantaged.

An overall long-term strategy for managing the coronavirus disease 2019 (COVID-19) pandemic is presented. This strategy will need to be maintained until herd immunity is achieved, hopefully through vaccination rather than natural infection. We suggest that a pure test-trace-isolate strategy is likely not practicable in most countries, and a degree of social distancing, ranging up to full lockdown, is the main public-health tool to mitigate the COVID-19 pandemic. Guided by reliable surveillance data, distancing should be continuously optimised down to the lowest sustainable level that guarantees a low and stable infection rate in order to balance its wide-ranging negative effects on public health. The qualitative mixture of social-distancing measures also needs to be carefully optimised in order to minimise social costs.

Coronaviruses primarily cause zoonotic infections, however in the past few decades several interspecies transmissions have occurred, the last one by SARS-CoV-2, causing COVID-19 pandemic, posing serious threat to global health. The SARS-CoV-2 spike (S) protein plays an important role in viral attachment, fusion and entry. However, other structural and non-structural SARS-CoV-2 proteins are potential influencers in virus pathogenicity. Among these proteins; Orf3, Orf8, and Orf10 show the least homology to SARSCoV proteins and therefore should be further studied for their abilities to modulate antiviral and inflammatory responses. Here, we discuss how SARS-COV-2 interacts with our immune system.

WHO convened an Advisory Group (AG) to consider the feasibility, potential value and limitations of establishing a closely-monitored challenge model of experimental SARS-CoV-2 infection and COVID-19 in healthy adult volunteers. The AG included experts in design, establishment and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (SARS-CoV-2's potential to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment" to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.

The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. In this review, we discuss the ongoing arguments in the literature about ACE2's role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.

Coronavirus Disease 2019 continues to spread and to date, no definitive treatment is available. Overcrowded and under-resourced healthcare centres have had to design different strategies to treat these patients, what includes the control of the electrocardiogram (ECG), as some drugs that have been used to treat this disease may prolong the QT interval as a side effect. During the COVID-19 outbreak, we designed a protocol for monitoring the QT interval using a portable device with Bluetooth connectivity. After a validation study with 50 patients, we found a very good correlation between the QT interval measured both with this device and with the conventional body surface ECG. In this article, we provide a brief overview of the protocol and then analyse the QT changes observed in a group of patients during their hospitalization and treatment for SARS-CoV-2 infection. 81 patients with confirmed SARS-CoV-2 infection were enrolled in the protocol (age 63.4 SD 17.2 years; 70.3% men), while being treated with lopinavir/ritonavir, azithromycin and hydroxychloroquine, both individually or combined. Ten patients developed long drug-related QT interval, and the QT prolongation was statically significant for all treatment schemes. All patients with drug induced QT prolongation corrected the QT interval following the indications of the protocol, and no patients died of arrhythmic causes after its implementation. In our experience, a protocol for the electrocardiographic monitoring of these patients minimizes the risk of iatrogenic QT interval prolongation and consequently reduces sudden death events, and for that purpose, portable devices like the one used in this protocol may constitute a useful tool to minimize the contact with such patients.

Although there is no reported genetic predisposition in contracting coronavirus disease 2019 (COVID-19), the mortality rate varies among different ethnic groups. Here we determined potential correlation between COVID-19 and spice consumption. The data from 163 countries including total cases, total deaths, and total recovered were analyzed. It was observed that there is a clear interrelated prevalence between the total number of COVID-19 cases per million population tested and the gram of spice supply per capita per day. Nations with lower consumptions of spices per capita showed greater number of COVID-19 cases per million population. This is not surprising as herbs and spices are well-known to boost immunity. Although the precise molecular mechanisms associated with spices and immunity are not completely understood, our findings led us to hypothesize that spice consumption plays a role in our ability to fight COVID-19; however, intensive research is needed to determine the translational value of these findings.

The impact of communicable diseases (infectious diseases) on human health is obvious. The sudden outbreak of COVID-19 (Corona Virus Disease 2019) has made people realise the threat of communicable diseases to mankind. As a city of many migrants, Zhuhai Special Economic Zone experienced great challenges brought about by the COVID-19 epidemic. Experience has been acquired from all aspects of this. A highly reactive, multifunctional and efficient emergency management system should be established, and the significance of information communication should be fully understood for the future.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reportedly infected otolaryngologists disproportionately in the early parts of the coronavirus disease 2019 pandemic. Recommendations from national and international health organizations suggest minimizing the use of flexible laryngoscopy as a result. Objective: To review evidence on the risks of aerosolization and transmission of SARS-CoV-2 from patients to health care personnel during endoscopy of the upper aerodigestive tract. Evidence Review: A comprehensive review of literature was performed on April 19, 2020, using the PubMed/MEDLINE (1966-April 2020), Embase (1975-April 2020), and Web of Science (1900-April 2020) databases. All English-language primary research studies were included if they assessed the transmission of SARS-CoV-2 or SARS-CoV-1 during procedures in the upper aerodigestive tract. The primary outcome measure was disease transmission among health care workers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for accuracy of reporting. Findings: The queries for SARS-CoV-2 and SARS-CoV-1 identified 6 articles for systematic review. No studies included in this review provided data for SARS-CoV-2 transmission during flexible laryngoscopy. A total of 204 of 1264 health care workers (16.1%) had procedure-specific infections of SARS-CoV-1 or SARS-CoV-2. Among those, 53 of 221 (24.0%) were exposed during intubation, 1 of 15 (6.7%) during bronchoscopy, and 1 of 1 (100%) during endoscopy-assisted intubation. Conclusions and Relevance: A substantial lack of research precludes formal conclusions about the safety of flexible laryngoscopy and transmission of SARS-CoV-2 from patients to health care workers. The use of appropriate precautionary measures and personal protective equipment appears to reduce the risk of transmission. Given the uncertainty in transmission and the known benefits of safety precautions, upper airway endoscopy may be reasonable to perform if precautionary steps are taken.

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.

*The third case of acute transverse myelitis due to SARS-CoV-2 reported in the world.*Possible inflammatory complications affecting the myelin in spinal cord.*We must be vigilant of the critical neurological illnesses associated with COVID-19.

BACKGROUND: If Parkinson's Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD patients. OBJECTIVE: In the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine. METHOD: A case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored. RESULTS: Out of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (p < 0.001) and diabetes (p = 0.049) compared to non-COVID-19. In non-COVID-19 PD population (n = 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases. CONCLUSION: A higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it.

The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucial aspect of infection, prognosis and associated case fatality rate. Individual genetic landscapes can contribute to understand Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) burden and can give information on how to fight virus spreading and the associated severe acute respiratory distress syndrome (ARDS). The spread and pathogenicity of the virus have become pandemic on specific geographic areas and ethnicities. Interestingly, SARS-CoV-2 firstly emerged in East Asia and next in Europe, where it has caused higher morbidity and mortality. This is a peculiar feature of SARS-CoV-2, different from past global viral infections (i.e., SARS-1 or MERS); it shares with the previous pandemics strong age- and sex-dependent gaps in the disease outcome. The observation that the severest COVID-19 patients are more likely to have a history of hypertension, diabetes and/or cardiovascular disease and receive Renin-Angiotensin-System (RAS) inhibitor treatment raised the hypothesis that RAS-unbalancing may have a crucial role. Accordingly, we recently published a genetic hypothesis on the role of RAS-pathway genes (ACE1, rs4646994, rs1799752, rs4340, rs13447447; and ACE2, rs2285666, rs1978124, rs714205) and ABO-locus (rs495828, rs8176746) in COVID-19 prognosis, suspecting inherited genetic predispositions to be predictive of COVID-19 severity. In addition, recently, Genome-Wide Association Studies (GWAS) found COVID-19-association signals at locus 3p21.31 (rs11385942) comprising the solute carrier SLC6A20 (Na+ and Cl- coupled transporter family) and at locus 9q34.2 (rs657152) coincident with ABO-blood group (rs8176747, rs41302905, rs8176719), and interestingly, both loci are associated to RAS-pathway. Finally, ACE1 and ACE2 haplotypes seem to provide plausible explanations for why SARS-CoV-2 have affected more heavily some ethnic groups, namely people with European ancestry, than Asians.

PURPOSE OF REVIEW: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19), documented in the literature thus far. RECENT FINDINGS: A small but growing literature documents cases of new onset neuro-ophthalmic disease, in the setting of COVID-19 infection. Patients with COVID-19 have experienced acute onset vision loss, optic neuritis, cranial neuropathies, and Miller Fisher syndrome. In addition, COVID-19 increases the risk of cerebrovascular diseases that can impact the visual system. SUMMARY: The literature on COVID-19 continues to evolve. Although COVID-19 primarily impacts the respiratory system, there are several reports of new onset neuro-ophthalmic conditions in COVID-infected patients. When patients present with new onset neuro-ophthalmic issues, COVID-19 should be kept on the differential. Testing for COVID-19 should be considered, especially when fever or respiratory symptoms are also present. When screening general patients for COVID-19-associated symptoms, frontline physicians can consider including questions about diplopia, eye pain, pain with extraocular movements, decreased vision, gait issues, and other neurologic symptoms. The presence of these symptoms may increase the overall probability of viral infection, especially when fever or respiratory symptoms are present. More research is needed to establish a causal relationship between COVID-19 and neuro-ophthalmic disease, and better understand pathogenesis.

Background: The Theory of Planned Behavior (TPB) and the Health Belief Model (HBM) were used to examine the opinion and behaviors of older adults regarding Coronavirus Disease 2019 (COVID-19), social distancing practices, stay-at-home orders, and hypothetical public policy messaging strategies. Method: A convenience sample (N = 242) of adults 60 and older in the state of Maryland took part in an online survey. Respondents filled out questions regarding demographic information, political affiliation, current social distancing behaviors, and TPB and HBM constructs in our proposed model. Linear regression analysis and analysis of covariance (ANCOVA) were conducted to test the model. Results: Attitude toward social isolation was affected by perceived benefits and barriers to social distancing measures, perceived severity of COVID-19, and political affiliation. Behavior intention was influenced by attitude, subjective norms, political affiliation, and messaging strategies. Conclusion: The study provides support for the conceptual model and has public policy implications as authorities begin to lift stay-at-home orders.

Aim: The outbreak of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic, with the main manifestations being of respiratory nature, including pneumonia. It is noteworthy that digestive symptoms are also observed in COVID-19 patients. In this article, we describe the immuno-inflammatory characteristics of low severity COVID-19 patients with digestive symptoms. Methods: Patients with mild symptoms of COVID-19 were split into three groups based on the patients' symptoms. The first group displayed digestive symptoms only, the second group displayed respiratory symptoms only, and the last group displayed both digestive and respiratory symptoms. Patients were discharged based on negative results of rRT-PCR testing for SARS-CoV-2 from at least two sequential respiratory tract specimens collected >/=24 hours apart. Multiorgan function and immuno-inflammatory characteristics were analyzed for all of the three groups. Results: Mild liver damage and activation of the immuno-inflammatory system were the most common abnormalities observed in patients with mild COVID-19 symptoms but no significant differences were found (P > 0.05). Patients with digestive symptoms were more likely to have slightly higher and later peak values of inflammatory cytokines during the subsequent course of disease (P < 0.05). In addition, a significant correlation between IL-2 and TNF level was found in the first group which included patients with digestive symptoms only (P < 0.05). Conclusions: Patients with mild cases of COVID-19 only displaying digestive symptoms are a special subtype. Patients in this group were more likely to have slightly higher and delayed peak values of inflammatory cytokines during the subsequent course of the disease. Prevention and clinical management of this type should be taken into consideration.

As the COVID-19 pandemic has developed, concern for invasive fungal infections in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) has emerged. We describe a clinical case of coronavirus disease (COVID-19) associated pulmonary aspergillus (CAPA) infection and acute respiratory distress syndrome (ARDS) with a good clinical outcome, in a previously well, non-immunocompromised Australian woman.

BACKGROUND: COVID-19 restrictions such as the closure of schools and parks, and the cancellation of youth sports and activity classes around the United States may prevent children from achieving recommended levels of physical activity (PA). This study examined the effects of the COVID-19 pandemic on PA and sedentary behavior (SB) in U.S. children. METHOD: Parents and legal guardians of U.S. children (ages 5-13) were recruited through convenience sampling and completed an online survey between April 25-May 16, 2020. Measures included an assessment of their child's previous day PA and SB by indicating time spent in 11 common types of PA and 12 common types of SB for children. Parents also reported perceived changes in levels of PA and SB between the pre-COVID-19 (February 2020) and early-COVID-19 (April-May 2020) periods. Additionally, parents reported locations (e.g., home/garage, parks/trails, gyms/fitness centers) where their children had performed PA and their children's use of remote/streaming services for PA. RESULTS: From parent reports, children (N = 211) (53% female, 13% Hispanic, Mage = 8.73 [SD = 2.58] years) represented 35 states and the District of Columbia. The most common physical activities during the early-COVID-19 period were free play/unstructured activity (e.g., running around, tag) (90% of children) and going for a walk (55% of children). Children engaged in about 90 min of school-related sitting and over 8 h of leisure-related sitting a day. Parents of older children (ages 9-13) vs. younger children (ages 5-8) perceived greater decreases in PA and greater increases in SB from the pre- to early-COVID-19 periods. Children were more likely to perform PA at home indoors or on neighborhood streets during the early- vs. pre-COVID-19 periods. About a third of children used remote/streaming services for activity classes and lessons during the early-COVID-19 period. CONCLUSION: Short-term changes in PA and SB in reaction to COVID-19 may become permanently entrenched, leading to increased risk of obesity, diabetes, and cardiovascular disease in children. Programmatic and policy strategies should be geared towards promoting PA and reducing SB over the next 12 months.

OBJECTIVE: To determine features that distinguish febrile young infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: Retrospective single-center study included febrile infants <57 days of age evaluated in the emergency department of Cohen Children's Medical Center of Northwell Health, New Hyde Park, New York, from March 1 to April 30 of 2018, 2019, and 2020. Sociodemographic and clinical features were compared between those seen during the 2020 coronavirus disease-2019 pandemic and previous years, as well as between infants with SARS-CoV-2 infection and infants without SARS-CoV-2 infection (SARS-CoV-2 negative or evaluated during 2018 and 2019). RESULTS: In all, 124 febrile infants <57 days of age were identified; 38 during the 2-month study period in 2018, 33 in 2019, and 53 in 2020. During 2020, fewer febrile infants had a serious bacterial infection or a positive respiratory viral panel than in prior years (6% vs 21% [P = .02]; 15% vs 53% [P < .001], respectively). SARS-CoV-2 was the most frequent pathogen detected in 2020; of 30 infants tested, 20 tested positive. Infants with SARS-CoV-2 were more likely to identify as Hispanic (P = .004), have public insurance or be uninsured (P = .01), exhibited lethargy (P = .02), had feeding difficulties (P = .002), and had lower white blood cell (P = .001), neutrophil (P < .001), and lymphocyte counts (P = .005) than the 81 infants without SARS-CoV-2 infection. None of the infants with SARS-CoV-2 had concurrent serious bacterial infection or detection of another virus. Overall, disease in infants with SARS-CoV-2 was mild. CONCLUSIONS: During the peak of the pandemic, SARS-CoV-2 was the predominant pathogen among febrile infants. Socioeconomic, historical, and laboratory features differed significantly between infants infected or not infected with SARS-CoV-2. None of the 20 infants with SARS-CoV-2 infection had an identified coviral or serious bacterial infection.

Acute viral respiratory infections are the main infectious disease in the world. In 2020, a new disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), became a global pandemic. The immune response to the virus depends on factors such as genetics, age and physical state, and its main input receptor is the angiotensin-converting enzyme 2. The practice of physical exercises acts as a modulator of the immune system. During and after physical exercise, pro- and anti-inflammatory cytokines are released, lymphocyte circulation increases, as well as cell recruitment. Such practice has an effect on the lower incidence, intensity of symptoms and mortality in viral infections observed in people who practice physical activity regularly, and its correct execution must be considered to avoid damage. The initial response is given mainly by type I interferons (IFN-I), which drive the action macrophages and lymphocytes, followed by lymphocyte action. A suppression of the IFN-I response has been noted in COVID-19. Severe conditions have been associated with storms of pro-inflammatory cytokines and lymphopenia, as well as circulatory changes and virus dispersion to other organs. The practice of physical activities strengthens the immune system, suggesting a benefit in the response to viral communicable diseases. Thus, regular practice of adequate intensity is suggested as an auxiliary tool in strengthening and preparing the immune system for COVID-19. Further studies are needed to associate physical exercise with SARS-CoV-2 infection.

Immunocompromised patients may be at increased risk to develop COVID-19 during the 2019 beta-coronavirus infection. We present the unique opportunity we had to monitor the liver, IL-6 and immune cell course before, during and after COVID-19 in a boy with autoimmune hepatitis (AIH) and type 1 diabetes (T1D). CD4 and CD8 T cells frequencies decreased because of prednisolone, followed by a plateauing increase whereas CD19CD20 B cell increased strongly and was unaffected by COVID-19 infection. Moreover, the percentage of activated CD8 T cells expressing HLA-DR (CD8HLA-DR) increased during COVID-19 and subsided after its clearance. Total regulatory T cells (Tregs: CD4CD25CD127FOXP3) remained stable. Although activated Tregs (CD4CD45RAFOXP3) strongly increased upon prednisolone, it decreased afterwards. Furthermore, regulatory B cells (Bregs: CD19CD20CD24CD38) declined sharply owing to prednisolone. Serum IL-6 remained undetectable at all times. We demonstrated for the first time immune monitoring in a child with AIH and T1D before, during and after COVID-19. We hypothesize that continuing with low level of prednisolone without azathioprine may have abrogated activated Tregs, Bregs and IL-6 production and therefore permitting the activation of CD8 T cells, clearing the virus.

On March 16, 2020, the French Society of Pharmacology and Therapeutics put online a national Question and Answer (Q&A) website, https://sfpt-fr.org/covid19 on the proper use of drugs during the COVID-19 pandemic. The working group 'Drugs and COVID-19' was composed of a scientific council, an editorial team, and experts in the field. The first questions were posted online during the first evening of home-confinement in France, March 17, 2020. Six weeks later, 140 Q&As have been posted. Questions on the controversial use of hydroxychloroquine and to a lesser extent concerning azithromycin have been the most consulted Q&As. Q&As have been consulted 226 014 times in 41 days. This large visibility was obtained through an early communication on Twitter, Facebook, traditional print, and web media. In addition, an early communication through the French Ministry of Health and the French National Agency for Medicines and Health Products Safety ANSM had a large impact in terms of daily number of views. There is a pressing need to sustain a public drug information service combining the expertise of scholarly pharmacology societies, pharmacovigilance network, and the Ministry of Health to quickly provide understandable, clear, expert answers to the general population's concerns regarding COVID-19 and drug use and to counter fake news.

BACKGROUND: In the context of the COVID-19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in-hospital death in patients with severe COVID-19. METHODS: All >/=18-year-old patients with confirmed severe COVID-19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in-hospital death. RESULTS: A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow-up period. The median age of non-survivors was significantly older than survivors (69 [64-76.5] years vs 64 [56-71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non-survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 x 10(9) /L (OR, 58.35; 95%CI: 2.16-1571.69; P = .016), hypersensitivity C-reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29-171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45-4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36-91.62; P = .024) were risk factors for in-hospital death. CONCLUSION: The risk factors of neutrophil count, hypersensitivity C-reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID-19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID-19.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel coronavirus that is involved in severe diarrhea disease in piglets, causing considerable agricultural and economic loss in China. The emergence of this new coronavirus increases the importance of understanding SADS-CoV as well as antivirals. Coronaviral proteases, including main proteases and papain-like proteases (PLP), are attractive antiviral targets because of their essential roles in polyprotein processing and thus viral maturation. Here, we describe the biochemical and structural identification of recombinant SADS papain-like protease 2 (PLP2) domain of nsp3. The SADS-CoV PLP2 was shown to cleave nsp1 proteins and also peptides mimicking the nsp2|nsp3 cleavage site and also had deubiquitinating and deISGynating activity by in vitro assays. The crystal structure adopts an architecture resembling that of PLPs from other coronaviruses. We characterize both conserved and unique structural features likely directing the interaction of PLP2 with the substrates, including the tentative mapping of active site and other essential residues. These results provide a foundation for understanding the molecular basis of coronaviral PLPs' catalytic mechanism and for the screening and design of therapeutics to combat infection by SADS coronavirus.

Most pediatric patients with COVID-19 are asymptomatic or show only mild symptoms. However, in the last two months, first in Europe and recently in the United States, a small number of children have developed a more severe inflammatory syndrome associated with COVID-19, which often leads to hospitalization and sometimes requires intensive care. A potential relationship was observed, especially between the occurrence of the Kawasaki disease and viral upper respiratory tract infections.

This case report describes our early radiological experiences of middle-aged patients with COVID-19 at Westmead Hospital, Sydney. We found limited relationship between initial CT imaging appearances and progression to severe disease. The most effective use of imaging in COVID-19 is yet to be determined.

The pandemic of coronavirus disease 2019 (COVID-19), a disease which causes severe lung injury and multiple organ damage, presents an urgent need for new drugs. The case severity and fatality of COVID-19 are associated with excessive inflammation, namely, a cytokine storm. Metformin, a widely used drug to treat type 2 diabetes (T2D) mellitus and metabolic syndrome, has immunomodulatory activity that reduces the production of proinflammatory cytokines using macrophages and causes the formation of neutrophil extracellular traps (NETs). Metformin also inhibits the cytokine production of pathogenic Th1 and Th17 cells. Importantly, treatment with metformin alleviates various lung injuries in preclinical animal models. In addition, a recent proteomic study revealed that metformin has the potential to directly inhibit SARS-CoV-2 infection. Furthermore, retrospective clinical studies have revealed that metformin treatment reduces the mortality of T2D with COVID-19. Therefore, metformin has the potential to be repurposed to treat patients with COVID-19 at risk of developing severe illness. This review summarizes the immune pathogenesis of SARS-CoV-2 and addresses the effects of metformin on inhibiting cytokine storms and preventing SARS-CoV-2 infection, as well as its side effects.

Objective: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. Methods: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. Results: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. Conclusion: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.

In this paper, a physicist's approach is given to support the necessity to wear surgical masks during the COVID-19 pandemics; they have become compulsory in Eastern countries, while in Western countries they are still an optional. My thesis is supported and described on the basis of a physicist's model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. The actual efficiency of FFP3 masks has been examined and found to be lower than expected.

In the past two decades, 7 coronaviruses have infected the human population, with two major outbreaks caused by SARS-CoV and MERS-CoV in the year 2002 and 2012, respectively. Currently, the entire world is facing a pandemic of another coronavirus, SARS-CoV-2, with a high fatality rate. The spike glycoprotein of SARS-CoV-2 mediates entry of virus into the host cell and is one of the most important antigenic determinants, making it a potential candidate for a vaccine. In this study, we have computationally designed a multi-epitope vaccine using spike glycoprotein of SARS-CoV-2. The overall quality of the candidate vaccine was validated in silico and Molecular Dynamics Simulation confirmed the stability of the designed vaccine. Docking studies revealed stable interactions of the vaccine with Toll-Like Receptors and MHC Receptors. The in silico cloning and codon optimization supported the proficient expression of the designed vaccine in E. coli expression system. The efficiency of the candidate vaccine to trigger an effective immune response was assessed by an in silico immune simulation. The computational analyses suggest that the designed multi-epitope vaccine is structurally stable which can induce specific immune responses and thus, can be a potential vaccine candidate against SARS-CoV-2.

Importance: Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective: To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants: This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures: SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results: Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance: In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

COVID-19 is an emerging infectious disease capable of causing severe pneumonia. We aimed to characterize a group of critically ill patients in a single-center study.This was a retrospective case series of 23 patients with confirmed COVID-19-related critical illness in the intensive care unit (ICU) of a hospital in Hangzhou Zhejiang Province between January 22 and March 20, 2020.Of the 23 critically ill patients, the median age was 66 years (interquartile range [IQR] 59-80 years). The median time from disease onset to ICU admission was 10 days (IQR 6-11 days), to mechanical ventilation (MV) was 11 days (IQR 7.75-13 days), to artificial liver plasma exchange was 12 days (IQR 9.75-14.75 days), and to extracorporeal membrane oxygenation (ECMO) was 22 days (IQR 17.5-30 days). Nine patients required high flow oxygen. Fourteen patients received MV. Six required ECMO. Nine received artificial liver plasma exchange. Mortality was 0 at day 28.Mortality was 0 at day 28 in our single-center study. Extracorporeal membrane oxygenation reduced the requirements for ventilator support. Artificial liver plasma exchange significantly reduced inflammatory cytokine levels. These supportive therapies helped to extend the patients' survival times and increase the chance of follow-up treatments.

With the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the whole world is suffering from atypical pneumonia which resulted in more than 559,047 deaths worldwide. In this time of crisis and urgency, the only hope comes from new candidate vaccines and potential antivirals. However, formulating new vaccines and synthesizing new antivirals is a laborious task. Therefore, considering the high infection rate and mortality due to COVID-19, utilization of previous information, and repurposing of existing drugs against valid viral targets has emerged as a novel drug discovery approach in this challenging time. The transmembrane spike (S) glycoprotein of coronaviruses (CoVs) which facilitates virus entry into the host cells, exists as homotrimeric form and is covered with N-linked glycans. S glycoprotein is known as the main target of antibodies having neutralizing potency and is also considered as an attractive target for therapeutic or vaccine development. Similarly, targeting of N-linked glycans of S glycoprotein envelop of CoV via carbohydrate-binding agents (CBAs) could serve as an attractive therapeutic approach for developing novel antivirals. CBAs from natural sources like lectins from plants, marine algae and prokaryotes and lectin mimics like Pradimicin-A (PRM-A) have shown antiviral activities against CoV and other enveloped viruses. However, the potential use of CBAs specifically lectins was limited due to unfavorable responses like immunogenicity, mitogenicity, hemagglutination, inflammatory activity, cellular toxicity, etc. Here, we have reviewed the current scenario of CBAs as antivirals against CoVs, presented strategies to improve the efficacy of CBAs against CoVs; and studied the molecular interactions between CBAs (lectins and PRM-A) with Man9 by molecular docking for potential repurposing against CoVs in general and the SARS-CoV-2 in particular.

Objectives: In the context of COVID-19 pandemic, the aim of this manuscript is to provide a standard of care of patients with ARDS for non-emergency medicine trained physicians who are not customary with mechanical ventilation.Methods: We conducted a systematic review of the literature to investigate the best practice recommendations regarding the mechanical ventilation of patients with ARDS.Conclusion: We summarized the principal strategies for lung-protective ventilation of patients with ARDS. This focus is particularly addressed to physicians who are not experienced in the invasive respiratory management of ARDS patients. Nevertheless, it remains fundamental to acknowledge that new insights concerning this quickly spreading illness become available on a regular base.

The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p=0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels (75-125nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.

PURPOSE: The COVID-19 infection is an aggressive viral illness with high risk of transmission during otolaryngology examination and surgery. Cholesteatoma is known for its potential to cause complications and scheduling of surgery during the pandemic must be done carefully. The majority of otological surgeries may be classified as elective and postponed at this time (e.g., stapedotomy, tympanoplasty); whereas, others are emergencies (e.g., complicated acute otitis media, complicated cholesteatoma with cerebral or Bezold's abscess, meningitis, sinus thrombosis) and require immediate intervention. What is the ideal time for the surgical management of Cholesteatoma during the COVID-19 pandemic? METHODS: Senior otologic surgeons from six teaching hospitals from various countries affected by the COVID-19 from around the world met remotely to make recommendations on reorganizing schedules for the treatment of cholesteatoma which has a risk of severe morbidity and mortality. The recommendations are based on their experiences and on available literature. RESULTS: Due to the high risk of infecting the surgical staff it is prudent to stop all elective ear surgeries and plan cholesteatoma surgery after careful selection of patients, based on the extent of the disease and available resources. Specific precautions including use of appropriate personal protection equipment should be followed when operating on all patients during the pandemic. To facilitate the decision-making in the management of cholesteatoma, timing for surgery can be divided into two categories with 3 and 2 sub-groups based on disease severity. CONCLUSIONS: Evidence on the timing of surgery of patients with cholesteatoma during the COVID-19 pandemic is lacking. This manuscript contains practical tips on how cholesteatoma surgery can be reorganized during this pandemic.

Aggressive tracing of contacts of confirmed cases is crucial to Taiwan's successful control of the early spread of COVID-19. As the pandemic lingers, an epidemiological investigation that can be conducted efficiently in a timely manner can help decrease the burden on the health personnel and increase the usefulness of such information in decision making. To develop a new tool that can improve the current practice of epidemiological investigation by incorporating new technologies in digital platform and knowledge graphs. To meet the various needs of the epidemiological investigation, we decided to develop an e-Outbreak Platform that provides a semi-structured, multifaceted, computer-aided questionnaire for outbreak investigation. There are three major parts of the platform: (1) a graphic portal that allows users to have an at-glance grasp of the functions provided by the platform and then choose the one they need; (2) disease-specific questionnaires that can accommodate different formats of the information, including text typing, button selection, and pull-down menu; and (3) functions to utilize the stored information, including report generation, statistical analyses, and knowledge graphs displaying contact tracing. When the number of outbreak investigation increases, the knowledge graphs can be extended to encompass other persons appearing in the same location at the same time, i.e., constituting a potential contact cluster. The information extracted can also be used to display the tracing on a map in animation. Overall, this system can provide a basis for further refinement that can be generalized to a variety of outbreak investigations.

This paper investigates the profile of COVID-19 cases in Hong Kong, highlighting the unique age structure of confirmed cases compared to other territories. While the majority of cases in most territories around the world have fitted an older age profile, our analysis shows that positive cases in Hong Kong have been concentrated among younger age groups, with the largest incidence of cases reported in the 15-24 age group. This is despite the population's rapidly aging structure and extremely high levels of population density. Using detailed case data from Hong Kong's Centre for Health Department and Immigration Department, we analyze the sex and age distribution of the confirmed cases along with their recent travel histories and immigration flows for the period January to April 2020. Our analysis highlights Hong Kong's high proportion of imported cases and large overseas student population in developing COVID-19 hotspot areas such as the United Kingdom. Combined with community action and targeted and aggressive early policy measures taken to contain the virus, these factors may have contributed to the uniquely younger age structure of COVID-19 cases in the city. Consequently, this young profile of confirmed cases may have prevented fatalities in the territory. Recent research has highlighted the importance of a demographic approach to understanding COVID-19 transmission and fatality rates. The experience in Hong Kong shows that while an older population age structure may be important for understanding COVID-19 fatality, it is not a given. From a social science perspective at least, there is 'no easy answer' to why one area should experience COVID-19 differently from another.

In nearly 1 month, with a rapidly expanding corona virus disease 2019 (COVID-19), telemedicine has been transformed into an essential service for delivering routine clinical care. This transformation occurred as a crisis management response-driven by the need to provide care for patients with physical distancing measures in place. However, the current rapid adoption of telemedicine presents a transitional state between one that existed before the pandemic and one that could potentially be better aligned with the delivery of a personalized model of care. Using the conceptual framework of digital translucence-situating virtual encounters with more nuanced information regarding patients-we describe the role of integrated remote monitoring and virtual care tools aligned with the patient's electronic health record for adapting telemedicine delivery post-COVID-19.

Great concerns have been raised on SARS-CoV-2 impact on men's andrological well-being, and one of the critically unanswered questions is whether it is present or not in the seminal fluid of infected subjects. The expression of ACE2 and TMPRSS2 in the testis and in the male genital tract allows speculations about a possible testicular involvement during the infection, possibly mediated by local and/or systemic inflammation that might allow a high viral load to overcome the hemato-testicular barrier. To date, few investigations have been carried out to ascertain the presence of SARS-CoV-2 in the seminal fluid with contrasting results. Furthermore, the cumulative number of subjects is far too low to answer the question unambiguously. Therefore, great caution is still needed when evaluating this data; otherwise, we risk unleashing unmotivated concerns in the scientific world with troublesome consequences in reproductive medicine.

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).

We report three critically ill pediatric patients (aged 6-10 years), presenting with features of multisystem inflammatory syndrome in children (MIS-C) from April 4 to May 10, 2020, to a tertiary-care center in New Jersey, United States. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were previously healthy. Clinical presentations were similar with fever, abdominal pain, gastrointestinal complaints, and/or rash. One patient had altered mental status with cerebrospinal fluid (CSF) findings consistent with aseptic meningitis. Laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin in all patients. All had low albumin levels. Evaluation for other infectious etiologies was negative. All of the patients were critically ill, requiring admission to the intensive care unit. All had circulatory shock and needed inotropes. Two patients had respiratory failure requiring advanced respiratory support and one had cardiac dysfunction. All patients received steroids, and two received intravenous immunoglobulin (IVIG). One patient received tocilizumab. None of the children died. MIS-C is a recently recognized pediatric illness spectrum in association with SARS-CoV-2 infection, and clinical characterization is essential for understanding disease mechanisms to inform clinical practice.

BACKGROUND: Since January 2020, when the pathogen causing the coronavirus disease was identified in humans, the literature on coronavirus disease 2019 (COVID-19) has grown exponentially to more than 4000 publications. There is the need to provide an update for each single medical discipline, including neurosurgery, to be used by single professionals or to be distributed through the neurosurgical community and to be used by governments in designing new scenario of care. METHODS: A review of the MEDLINE database was performed on April 13, 2020. Search terms included "COVID-19," "neurosurgery," and "surgery." A review of documents published on the webpage of the WFNS (World Federation of Neurosurgical Societies) and of the 5 continental associations of neurosurgical societies, AANS (American Association of Neurological Surgeons), AASNS (Asian Australasian Society of Neurological Surgeons), CAANS (Continental Association of African Neurosurgical Societies), EANS (European Association of Neurosurgical Societies), and FLANC (Latin American Federation of Neurosurgical Societies), representing the 119 national neurosurgical societies around the world, was performed. RESULTS: The literature search yielded 38 results that were manually reviewed. Fourteen manuscripts were considered eligible. They described suggestions and considerations to optimize care of neurosurgical patients, editorials on operational models, perspectives from neurosurgical departments, letters to the editor describing experiences on how to help medical staff to be prepared in advance for pandemic situations, and descriptions of regional or departmental models and/or organizational schemes. The webpages of the searched societies reported a total of 57 documents. CONCLUSIONS: The neurosurgical scientific community has promptly reacted to the COVID-19 outbreak by producing a growing number of documents that could serve as guidance for neurosurgeons all over the world. Neurosurgical societies will represent the key institutions for guiding the neurosurgical community to overcome the COVID-19 crisis.

As part of any plan to lift or ease the confinement restrictions that are in place in many different countries, there is an urgent need to increase the capacity of laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Detection of the viral genome through reverse transcription-quantitative PCR (RT-qPCR) is the gold standard for this virus; however, the high demand of the materials and reagents needed to sample individuals, purify the viral RNA, and perform the RT-qPCR has resulted in a worldwide shortage of several of these supplies. Here, we show that directly lysed saliva samples can serve as a suitable source for viral RNA detection that is less expensive and can be as efficient as the classical protocol, which involves column purification of the viral RNA. In addition, it bypasses the need for swab sampling, decreases the risk of the health care personnel involved in the testing process, and accelerates the diagnostic procedure.

Objective: Saudi Arabia ranks second in the number of coronavirus disease 2019 (COVID-19) cases in the Eastern Mediterranean region. It houses the two most sacred religious places for Muslims: Mecca and Medina. It is important to know what the trend in case numbers will be in the next 4-6 months, especially during the Hajj pilgrimage season. Methods: Epidemiological data on COVID-19 were obtained from the Saudi Arabian Ministry of Health. A susceptible-exposed-infectious-recovered (SEIR) prediction model was constructed to predict the trend in COVID-19 in Saudi Arabia in the next 6 months. Findings: The model predicts that the number of active cases will peak by 22 May 2020. The cumulative infected cases are predicted to reach 70,321 at that time. The total number of infected individuals is estimated reach to 114,580 by the end of the pandemic. Conclusion: Our estimates show that by the time the Hajj season commences in Saudi Arabia, the pandemic will be in the midst of its deceleration phase (phase 3). This information will likely be useful to policymakers in their management of the outbreak.

The Journal of Ethnobiology and Ethnomedicine (JEET), throughout its 15 years of existence, has tried to provide a respected outlet for scientific knowledge concerning the inextricable links between human societies and nature, food, and health. Ethnobiology and ethnomedicine-centred research has moved at the (partially artificial and fictitious) interface between nature and culture and has investigated human consumption of wild foods and wild animals, as well as the use of wild animals or their parts for medicinal and other purposes, along with the associated knowledge, skills, practices, and beliefs. Little attention has been paid, however, to the complex interplay of social and cultural reasons behind the increasing pressure on wildlife. The available literature suggest that there are two main drivers that enhance the necessary conditions for infectious diseases to cross the species barrier from wild animals to humans: (1) the encroachment of human activities (e.g., logging, mining, agricultural expansion) into wild areas and forests and consequent ecological disruptions; and, connected to the former, (2) the commodification of wild animals (and natural resources in general) and an expanding demand and market for wild meat and live wild animals, particularly in tropical and sub-tropical areas. In particular, a crucial role may have been played by the bushmeat-euphoria and attached elitist gastronomies and conspicuous consumption phenomena. The COVID-19 pandemic will likely require ethnobiologists to reschedule research agendas and to envision new epistemological trajectories aimed at more effectively mitigating the mismanagement of natural resources that ultimately threats our and other beings' existence.

This is an opinion piece on the role of POCUS in COVID-19, with a focus on lung ultrasound. It is not an instructional essay. Crisis management in medicine has often been likened to crisis management in the aviation industry. The important difference between pilots and clinicians being that the clinician's life was not in imminent danger, should one fail. The clinician did not have the same emotional urgency as the pilot. The COVID-19 pandemic has changed this, clinicians are now faced with the need to make urgent decisions whilst exposed to some personal risk. Whether to embrace POCUS and lung ultrasound during this pandemic is an important decision. Whilst there are clear advantages, poorly considered overzealous uptake it is not without hazard, opportunity cost and potential risk to patient and clinician.

OBJECTIVE: To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. DESIGN: A prospective, single-center observational study was carried out. SETTING: Intensive care. PATIENTS: Patients admitted due to COVID-19 and respiratory failure. INTERVENTIONS: None. VARIABLES: Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p<0.05. RESULTS: A total of 43 patients were included (G1=28 [65.1%]; G2=10 [23.3%] and G3=5 [11.6%]), with a mean age of 65 years (range: 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285]; p=0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294]; p=0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). CONCLUSIONS: Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. .

PURPOSE OF REVIEW: Novel coronavirus disease 2019 (COVID-19) has been associated with an increased risk of arterial and venous thromboembolic (VTE) diseases. However, there is a limited amount of data regarding the prevention and management of VTE in severe hospitalized COVID-19 patients. RECENT FINDINGS: In this article, we review currently available clinical data, and mechanisms for COVID-associated coagulopathy, and propose algorithms for screening, prevention (including extended-duration prophylaxis), and treatment of these patients. Although these recommendations are subject to change given rapidly evolving data, we provide a framework that can guide clinicians in managing thrombotic complications in this challenging condition.

The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend.

BACKGROUND: Thymosin alpha 1 (Talpha1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and the mechanism of Talpha1 treatment for COVID-19 patients are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe COVID-19 cases admitted to 2 hospitals in Wuhan, China, from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells from COVID-19 patients was measured by T-cell receptor excision circles (TRECs). The levels of T-cell exhaustion markers programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with the untreated group, Talpha1 treatment significantly reduced the mortality of severe COVID-19 patients (11.11% vs 30.00%, P = .044). Talpha1 enhanced blood T-cell numbers in COVID-19 patients with severe lymphocytopenia. Under such conditions, Talpha1 also successfully restored CD8+ and CD4+ T-cell numbers in elderly patients. Meanwhile, Talpha1 reduced PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients compared with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells were roughly parallel to the rise of TRECs. CONCLUSIONS: Talpha1 treatment significantly reduced mortality of severe COVID-19 patients. COVID-19 patients with counts of CD8+ T cells or CD4+ T cells in circulation less than 400/muL or 650/muL, respectively, gained more benefits from Talpha1. Talpha1 reversed T-cell exhaustion and recovered immune reconstitution through promoting thymus output during severe acute respiratory syndrome-coronavirus 2 infection.

In this study, efficacy and safety of interferon (IFN) beta-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (>/=18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN beta-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN beta-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN beta-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN beta-1b.

AIM: To compile recommendations and evidence on the practical management of pregnant women with COVIC-19 in order to clarify standards of obstetric care in the face of this new disease. METHODS: Scoping review based on literaature searches in national and international health science databases (Pubmed/Medline, Biblioteca virtual en salud (BVS), Scielo, COCHRANE and CUIDEN) and websites, and additionally by a "snowball" system. MeSH terms were used: "COVID-19", "Pregnancy", "Delivery, Obstetric" "Pregnant Women" and "Maternal". As limits in the search Spanish and English languages were selected. No limits were established in relation to the year of publication or type of article. RESULTS: A total of 49 documents and articles were detected, of which 27 were analyzed, 18 were used, and 9 were discarded because they did not contain practical recommendations. The recommendations were grouped into 9 subjects: Prevention of infection in pregnant women, Prevention of infection in health care personnel attending pregnant women, Form of presentation and severity in pregnant women, Maternal-fetal transmission (vertical and perinatal), Maternal-fetal control of the pregnant woman infected with COVID-19, Control of the severely pregnant woman with COVID-19, Treatment of the pregnant woman with COVID-19, Management and route of termination of labor, Neonatal outcomes in women with COVID-19 and Breastfeeding. CONCLUSIONS: Lack of strong evidence to support many of the recommendations for pregnant women with COVID-19, as they are based on previous experience with SARS-CoV and MERS-CoV infections. Further studies are needed to confirm the appropriateness of many of the recommendations and guidelines for action in the specific case of pregnant women and COVIC-19.

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seeing a rapid increase in infected patients worldwide. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses, but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. In this review, we discuss the immunopathology of COVID-19, its potential mechanisms, and clinical implications to aid the development of new therapeutic strategies against COVID-19.

COVID-19 has now become a pandemic. It has spread from Wuhan, China, in December 2019 to a large number of countries within three months. The objective of this work is to report the initial experience with epidemiologic and clinical features, as well as with the management of COVID-19 patients in India. This is a descriptive case series of the first 21 COVID-19 infected patients confirmed with polymerase chain reaction (PCR) and admitted to a tertiary care centre in India from 01.02.2020 to 19.03.2020. Clinical, laboratory, and radiologic data were collected, including age, sex, nationality, travel history, symptoms, duration of stay, and comorbidities. The mean age of the population was 40.3 years with a male preponderance. Thirteen (62%) patients had recent travel history outside India in the previous 30 days, two thirds of whom had travelled to Italy. The most common symptoms were fever and cough (42.9%) followed by sore throat, headache and breathlessness. Vital and laboratory parameters were preserved in all patients and none of them required ventilatory support. Among the first 21 patients diagnosed with COVID-19 infection in India, the typical clinical presentation consisted in a mild upper respiratory tract infection predominantly affecting the young male population. One patient required supplemental oxygen. All patients recovered with no residual symptoms. *The Safdarjung Hospital COVID 2019 working group: Nitesh Gupta, Sumita Agrawal, Pranav Ish, Suruchi Mishra, Rajni Gaind, Ganapathy Usha, Balvinder Singh, Manas Kamal Sen, Shibdas Chakrabarti (Consultant and Head, Pulmonary Medicine); NK Gupta (Professor, Pulmonary medicine); Dipak Bhattacharya (Consultant, Pulmonary medicine); Rohit Kumar (Assistant Professor, Pulmonary Medicine); Siddharth R. Yadav (Assistant Professor, Pulmonary Medicine); Rushika Saksena (Specialist, Microbiology); Rojaleen Das (Assistant Professor, Microbiology); Vikramjeet Dutta (Assistant Professor, Microbiology); Anupam Kr Anveshi (Senior Resident, Microbiology); Santvana Kohli (Assistant Professor, Anaesthesiology); Naveen KV (Assistant Professor, Anaesthesiology); Amandeep Jaswal (Assistant Professor, Anaesthesiology).

The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 infection, two recent studies demonstrate that kidney impairment in hospitalized COVID-19 patients is common, and that kidney involvement is associated with high risk of in-hospital death. Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys. We propose that sodium intake and status should be monitored carefully during severe COVID-19 infections, and that low sodium intake be corrected early in its course, despite a potential conflict regarding common dietary recommendations to restrict dietary sodium intake in patients with hypertension, diabetes, and kidney disease.

The coronavirus disease-19 pandemic (COVID-19), which appeared in China in December 2019 and rapidly spread throughout the world, has forced clinicians and scientists to take up extraordinary challenges. This unprecedented situation led to the inception of numerous fundamental research protocols and many clinical trials. It quickly became apparent that although COVID-19, in the vast majority of cases, was a benign disease, it could also develop a severe form with sometimes fatal outcomes. Cytokines are central to the pathophysiology of COVID-19; while some of them are beneficial (type-I interferon, interleukin-7), others appear detrimental (interleukin-1beta, -6, and TNF-alpha) particularly in the context of the so-called cytokine storm. Yet another characteristic of the disease has emerged: concomitant immunodeficiency, notably involving impaired type-I interferon response, and lymphopenia. This review provides an overview of current knowledge on COVID-19 immunopathology. We discuss the defective type-I IFN response, the theoretical role of IL-7 to restore lymphocyte repertoire, as well as we mention the two patterns observed in severe COVID-19 (i.e. interleukin-1beta-driven macrophage activation syndrome vs. interleukin-6-driven immune dysregulation). Next, reviewing current evidence drawn from clinical trials, we examine a number of cytokine and anti-cytokine therapies, including interleukin-1, -6, and TNF inhibitors, as well as less targeted therapies, such as corticosteroids, chloroquine, or JAK inhibitors.

A novel coronavirus (SARS-CoV-2, formerly known as nCoV-2019) that causes an acute respiratory disease has emerged in Wuhan, China and spread globally in early 2020. On January the 30th, the World Health Organization (WHO) declared spread of this virus as an epidemic and a public health emergency. With its highly contagious characteristic and long incubation time, confinement of SARS-CoV-2 requires drastic lock-down measures to be taken and therefore early diagnosis is crucial. We analysed transcriptome of SARS-CoV-2 infected human lung epithelial cells, compared it with mock-infected cells, used network-based reporter metabolite approach and integrated the transcriptome data with protein-protein interaction network to elucidate the early cellular response. Significantly affected metabolites have the potential to be used in diagnostics while pathways of protein clusters have the potential to be used as targets for supportive or novel therapeutic approaches. Our results are in accordance with the literature on response of IL6 family of cytokines and their importance, in addition, we find that matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) with keratan sulfate synthesis pathway may play a key role in the infection. We hypothesize that MMP9 inhibitors have potential to prevent "cytokine storm" in severely affected patients.

Up to now, little is known about the detailed immune profiles of COVID-19 patients from admission to discharge. In this study we retrospectively reviewed the clinical and laboratory characteristics of 18 COVID-19 patients from January 30, 2020 to February 21, 2020. These patients were divided into two groups; group 1 had a severe acute respiratory syndrome coronavirus 2 nucleic acid-positive duration for more than 15 days (n = 6) and group 2 had a nucleic acid-positive duration for less than 15 days (n = 12). Group 1 patients had lower level of peripheral blood lymphocytes (0.40 vs. 0.78 x10(9)/L, p = 0.024) and serum potassium (3.36 vs. 3.79 mmol/L, p = 0.043) on admission but longer hospitalization days (23.17 vs. 15.75 days, p < 0.001) compared to Group 2 patients. Moreover, baseline level of lymphocytes (r = -0.62, p = 0.006) was negatively correlated with the nucleic acid-positive duration. Additionally, lymphocytes (420.83 vs. 1100.56 /muL), T cells (232.50 vs. 706.78 /muL), CD4(+) T cells (114.67 vs. 410.44 /muL), and CD8(+) T cells (94.83 vs. 257.44 /muL) in the peripheral blood analyzed by flow cytometry were significantly different between Group 1and Group 2. Furthermore, there was also a negative correlation between lymphocytes (r = -0.54, p = 0.038) or T cells (r = -0.55, p = 0.034) at diagnosis and the nucleic acid-positive duration, separately. In conclusion, the patients with nucleic acid-positive >/= 15 days had significantly decreased lymphocytes, T cell and its subsets compared to those who remained positive for less than 15 days.

The first pandemic of the coronavirus family was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019. As a result of the pandemic critical condition, specialized orthopedic services were obviously affected. To respond properly, we initiated a series of strategic measures, aiming at the safety of staff, minimizing the exposure, and prevention of possible disruption in providing services.

BACKGROUND: Steroid use for COVID-19 is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by SARS-CoV-2. This study aimed at evaluating at evaluating the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: Parallel, double-blind, placebo-controlled, randomized, phase IIb clinical trial was performed with hospitalized patients aged >/= 18 years with clinical, epidemiological and/or radiological suspected COVID-19, at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution), twice daily, for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. ClinicalTrials Identifier NCT04343729. FINDINGS: From April 18 to June 16, 2020, 647 patients were screened, 416 randomized, and 393 analyzed as mITT, MP in 194 and placebo in 199 individuals. SARS-CoV-2 infection was confirmed by RT-PCR in 81.3%. Mortality at day 28 was not different between groups. A subgroup analysis showed that patients over 60 years in the MP group had a lower mortality rate at day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until day 7. CONCLUSION: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population.

PURPOSE: The COVID-19 pandemic is importantly affecting the orthopaedic practice all over the world with Northern Italy being the first European area that faced the worst scenario. In this study, the changes in clinical practice occurred in an orthopaedic center in Milan are described. METHODS: Number and type of admissions, outpatients cancelled and preserved, emergency room, and intensive care unit activities have been analyzed in the timeframe of seven weeks since the beginning of the pandemic (from February 24th to April 10th) and compared with the same period in 2019. RESULTS: The planned surgical admissions declined from 2172 in 2019 to 664 in 2020 (69.42%, p < 0.0001), while emergencies increased from 158 to 268 (69.62%). The rehabilitation admissions declined from 414 to 69 (83.33%). The overall admission decreased by 63.52%, the trend showed a drop in the last weeks. Surgery performed in the COVID-19 operating room increased by 16.7% in the last week. Seven deaths occurred (0.7% of all orthopaedics and trauma admissions) compared with four (0.1%) which happened in the same period in 2019 (p = 0.004). Six of these patients were suffering from COVID-19. A total of 23,580 outpatients (93.8%) were cancelled. Emergency room consultations declined by 68.14% and 63.47% among white and green priority, respectively, while increased by 25% and 100% among yellow and red, respectively. CONCLUSION: These numbers show the radical changed scenario in an orthopaedic center in Milan during COVID-19 pandemic. Elective surgery declined rapidly going close to zero, outpatient admissions were restricted to cases that cannot be postponed, while emergencies increased due to the role played by the hospital as referral orthopaedic centre during the pandemic. The still ongoing emergency will have important impacts on the overall orthopaedic healthcare management for the next months.

BACKGROUND: The role of the renin-angiotensin-aldosterone system in COVID-19 is controversially discussed. SARS-CoV-2 enters host cells by binding to angiotensin-converting enzyme 2 and activity of the renin-angiotensin-aldosterone system may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. METHODS: In this prospective single-center study, we determined the serum levels of ACE-2, angiotensin II and aldosterone in patients with COVID-19 compared to control patients presenting with similar symptoms in the emergency unit. RESULTS: We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups. CONCLUSIONS: In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19.

BACKGROUND: The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 has caused widespread transmission around the world. As new epicentres in Europe and America have arisen, of particular concern is the increased number of imported coronavirus disease 2019 (COVID-19) cases in Africa, where the impact of the pandemic could be more severe. We aim to estimate the number of COVID-19 cases imported from 12 major epicentres in Europe and America to each African country, as well as the probability of reaching 10,000 cases in total by the end of March, April, May, and June following viral introduction. METHODS: We used the reported number of cases imported from the 12 major epicentres in Europe and America to Singapore, as well as flight data, to estimate the number of imported cases in each African country. Under the assumption that Singapore has detected all the imported cases, the estimates for Africa were thus conservative. We then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until 10,000 cases are reached or the end of June, whichever is earlier. Specifically, 1,000 simulations were run separately under four different combinations of parameter values to test the sensitivity of our results. RESULTS: We estimated Morocco, Algeria, South Africa, Egypt, Tunisia, and Nigeria as having the largest number of COVID-19 cases imported from the 12 major epicentres. Based on our 1,000 simulation runs, Morocco and Algeria's estimated probability of reaching 10,000 cases by end of March was close to 100% under all scenarios. In particular, we identified countries with less than 1,000 cases in total reported by end of June whilst the estimated probability of reaching 10,000 cases by then was higher than 50% even under the most optimistic scenario. CONCLUSIONS: Our study highlights particular countries that are likely to reach (or have reached) 10,000 cases far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic.

A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.

Purpose: Coronavirus disease 2019 (COVID-19) is an emerging disease that was first reported in Wuhan city, the capital of Hubei province in China, and has subsequently spread worldwide. Risk factors for mortality have not been well summarized. Current meta-analysis of retrospective cohort studies was done to summarize available findings on the association between age, gender, comorbidities and risk of death from COVID-19 infection.Methods: Online databases including Web of Science, PubMed, Scopus, Cochrane Library and Google scholar were searched to detect relevant publications up to 1 May 2020, using relevant keywords. To pool data, random-effects model was used. Furthermore, sensitivity analysis and publication bias test were also done.Results: In total, 14 studies with 29,909 COVID-19 infected patients and 1445 cases of death were included in the current meta-analysis. Significant associations were found between older age (>/=65 vs <65 years old) (pooled ORs = 4.59, 95%CIs = 2.61-8.04, p < .001), gender (male vs female) (pooled ORs = 1.50, 95%CIs = 1.06-2.12, p = .021) and risk of death from COVID-19 infection. In addition, hypertension (pooled ORs = 2.70, 95%CIs = 1.40-5.24, p = .003), cardiovascular diseases (CVDs) (pooled ORs = 3.72, 95%CIs = 1.77-7.83, p = .001), diabetes (pooled ORs = 2.41, 95%CIs = 1.05-5.51, p = .037), chronic obstructive pulmonary disease (COPD) (pooled ORs = 3.53, 95%CIs = 1.79-6.96, p < .001) and cancer (pooled ORs = 3.04, 95%CIs = 1.80-5.14, p < .001), were associated with higher risk of mortality.Conclusions: Older age (>/=65 years old), male gender, hypertension, CVDs, diabetes, COPD and malignancies were associated with greater risk of death from COVID-19 infection. These findings could help clinicians to identify patients with poor prognosis at an early stage.

AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.

COVID-19 has impacted how we deliver care to patients, and much remains unknown regarding optimal management of respiratory failure in this patient population. There are significant controversies regarding tracheostomy in patients with COVID-19 related to timing, location of procedure, and technique. In this narrative review, we explore the recent literature, publicly available guidelines, protocols from different institutions, and clinical reports to provide critical insights on how to deliver the most benefit to our patients while safeguarding the health care force. Consensus can be reached that patients with COVID-19 should be managed in a negative-pressure environment with proper personal protective equipment, and that performing tracheostomy is a complex decision that should be made through multidisciplinary discussions considering patient prognosis, institutional resources, staff experience, and risks to essential health care workers. A broad range of practices exist because there is no conclusive guidance regarding the optimal timing or technique for tracheostomy.

Thrombotic complications associated with coronavirus disease 2019 (COVID-19) have been described; these have mainly included venous thromboembolic events. Limited literature is available regarding arterial thrombosis. Acute limb ischemia is associated with severe complications that can result in significant morbidity and mortality. Herein, we report 3 cases of COVID-19 infection complicated by arterial thrombosis in the form of acute limb ischemia. Our case series adds to the limited literature regarding arterial thrombosis.

In the case of pandemic crisis situations, a crucial lack of protective material such as protective face masks for healthcare professionals can occur. A proof of concept (PoC) and prototype are presented, demonstrating a reusable custom-made three-dimensionally (3D) printed face mask based on materials and techniques (3D imaging and 3D printing) with global availability. The individualized 3D protective face mask consists of two 3D-printed reusable polyamide composite components (a face mask and a filter membrane support) and two disposable components (a head fixation band and a filter membrane). Computer-aided design (CAD) was used to produce the reusable components of the 3D face mask based on individual facial scans, which were acquired using a new-generation smartphone with two cameras and a face scanning application. 3D modelling can easily be done by CAD designers worldwide with free download software. The disposable non-woven melt-blown filter membrane is globally available from industrial manufacturers producing FFP2/3 protective masks for painting, construction, agriculture, and the textile industry. Easily available Velcro fasteners were used as a disposable head fixation band. A cleaning and disinfection protocol is proposed. Leakage and virological testing of the reusable components of the 3D face mask, following one or several disinfection cycles, has not yet been performed and is essential prior to its use in real-life situations. This PoC should allow the reader to consider making and/or virologically testing the described custom-made 3D-printed face masks worldwide. The surface tessellation language (STL) format of the original virtual templates of the two reusable components described in this paper can be downloaded free of charge using the hyperlink (Supplementary Material online).

BACKGROUND: Health-care workers (HCWs) could be at increased occupational risk for SARS-CoV-2 infection. Information regarding prevalence and risk factors for adverse outcomes in HCWs is scarce in Mexico. Here, we aimed to explore prevalence of SARS-CoV-2, symptoms, and risk factors associated with adverse outcomes in HCWs in Mexico City. METHODS: We explored data collected by the National Epidemiological Surveillance System in Mexico City. All cases underwent real-time RT-PCR test. We explored outcomes related to severe COVID-19 in HCWs and the diagnostic performance of symptoms to detect SARS-CoV-2 infection in HCWs. RESULTS: As of July 5 th, 2020, 35,095 HCWs were tested for SARS-CoV-2 and 11,226 were confirmed (31.9%). Overall, 4,322 were nurses (38.5%), 3,324 physicians (29.6%), 131 dentists (1.16%) and 3,449 laboratory personnel and other HCWs (30.8%). After follow-up, 1,009 HCWs required hospitalization (9.00%), 203 developed severe outcomes (1.81%), and 93 required mechanical-ventilatory support (0.82%). Lethality was recorded in 226 (2.01%) cases. Symptoms associated with SARS-CoV-2 positivity were fever, cough, malaise, shivering, myalgias at evaluation but neither had significant predictive value. We also identified 341 asymptomatic SARS-CoV-2 infections (3.04%). Older HCWs with chronic non-communicable diseases, pregnancy, and severe respiratory symptoms were associated with higher risk for adverse outcomes. Physicians had higher risk for hospitalization and for severe outcomes compared with nurses and other HCWs. CONCLUSIONS: We report a high prevalence of SARS-CoV-2 infection in HCWs in Mexico City. No symptomatology can accurately discern HCWs with SARS-CoV-2 infection. Particular attention should focus on HCWs with risk factors to prevent adverse outcomes and reduce infection risk.

OBJECTIVE: To perform an ecological study to analyze the geospatial distribution of neurosurgeons >/=60 years old and compare these data with the spread of 2019 novel coronavirus disease (COVID-19) across the United States. METHODS: Data regarding distribution of COVID-19 cases were collected from the Environmental Systems Research Institute, and demographic statistics were collected from the American Association of Medical Colleges 2019 State Workforce Reports. These figures were analyzed using geospatial mapping software. RESULTS: As of July 5, 2020, the 10 states with the highest number of COVID-19 cases showed older neurosurgical workforce proportions (the proportion of active surgeons >/=60 years old) of 20.6%-38.9%. Among states with the highest number of COVID-19 deaths, the older workforce proportions were 25.0%-43.4%. Connecticut demonstrated the highest with 43.4% of neurosurgeons >/=60 years old. CONCLUSIONS: Regional COVID-19 hotspots may coincide with areas where a substantial proportion of the neurosurgical workforce is >/=60 years old. Continuous evaluation and adjustment of local and national clinical practice guidelines are warranted throughout the pandemic era.

Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic "focusing event". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a "policy window" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.

The coronavirus infectious disease 2019 (COVID-19) pandemic has put enormous pressure on health care systems around the world. Dentistry has had to adjust to the new epidemic situation to not only bring relief to suffering patients but also to avoid becoming a source of SARS-CoV-2 transmission. METHODS: A comprehensive, cross-sectional survey was conducted between April 6 and 16, 2020 among 875 Polish dental practitioners. The aim of the research was to assess dentists' attitudes and professional approaches resulting from the COVID-19 pandemic. RESULTS: 71.2% of dentists who responded to the questionnaire decided to suspend their clinical practice during that particular time. The main factors for this fact were the shortage of personal protective equipment (PPE), the respondents' subjective perceptions of the risk of COVID-19 contraction and a general feeling of anxiety and uncertainty regarding the COVID-19 situation. The authors observed a significant decrease in the number of patients admitted weekly in April 2020 (12.06; SD, 11.55) in comparison to that in the time before the state of pandemic was declared on March 11, 2020 (49.21; SD, 24.97). CONCLUSIONS: Due to the unpreparedness of the dental sector, both in national health and private settings, most of the Polish dentists decided to voluntarily suspend their clinical practice in order to mitigate the spread of the disease. The COVID-19 outbreak has revealed numerous shortcomings in the dental care system, especially regarding the insufficient coordination of health services related to the pandemic and lack of advanced PPE. This has led to an overwhelming feeling of fear, confusion and anxiety among dental professionals in Poland and a sudden decrease in the number of performed dental procedures. Hopefully enriched with the recent experience and due to the implementation of proper strategic and long-term measures, dental practitioners will be better prepared and adapted to global health care disruptions in the future.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain that was discovered in 2019 and has not been previously identified in humans. On December 31st 2019 World Health Organization (WHO) was informed of a cluster of cases with pneumonia of unknown origin from Wuhan City, Hubei province of China. The WHO announced in February 2020 that COVID-19 is the official name of the coronavirus diseases. A total of 519,899 confirmed cases with 23,592 deaths linked to this pathogen as on March 27, 2020 have been reported. Due to increasing number of infected people across the continents and huge loss to human life, the WHO has declared the novel COVID-19 outbreak a pandemic. A pandemic is defined as the "worldwide spread" of a new disease. Currently, no COVID-19 specific treatments have been approved by the United States Food and Drug Administration (US-FDA). However, the current treatment options include hydroxychloroquine, tocilizumab, remdesivir, lopinavir-ritonavir (Kaletra(R)), and nitazoxanide. In recent past, some natural herbal compounds have demonstrated encouraging anti-viral properties. This article attempted to summarize available information on the reported anti-viral activity of some natural products.

BACKGROUND: The ongoing COVID-19 pandemic has greatly impacted the health services worldwide, challenging the way modern medicine has been practiced for decades. AIM: The present study documents an institutional experience on its impact on cytology services. MATERIALS & METHODS: The cytology samples received during lock down period in India (24 March to 17 May 2020) were analysis and compared to the samples received during the same time frame in year 2019. RESULTS: The data revealed an overall 92.6% reduction in cytology samples received. All sample types were reduced with a statically significant reduction in thyroid cytology samples (P-value: .023). There was relative increase in breast and lymph node samples; however, this relative increase was not statistically significant. The malignancy rate also significantly increased by 34.1% accompanied by decrease in neoplastic category among the samples received during COVID-19 lockdown period. Breast samples remain the most frequent sample type both in pre-COVID-19 and COVID-19 periods. Majority of fine-needle aspiration done in these cases, during the lockdown period, were either in cases for recurrence or primary diagnosis. CONCLUSION: Prioritization of samples, proper precautions and triaging of patients before procedure helped in carrying out this procedure safely.

The global pandemic involving severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) has stretched the limits of science. Ever since it emerged from the Wuhan province in China, it has spread across the world and has been fatal to about 4% of the victims. This position statement of the Indian Society of Critical Care Medicine represents the collective opinion of the experts chosen by the society. How to cite this article: Mehta Y, Chaudhry D, Abraham OC, Chacko J, Divatia J, Jagiasi B, et al. Critical Care for COVID-19 Affected Patients: Position Statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020;24(4):222-241.

In response to the COVID-19 pandemic, in April 2020 the Association for Value-Based Cancer Care (AVBCC) introduced a series of webcasts titled "COVID-19 Impact on the Cancer Care Delivery Ecosystem." The following articles highlight some of the presentations that addressed the impact of the novel coronavirus on healthcare stakeholders during and beyond this pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of pandemic coronavirus disease 2019 (COVID-19). So far, no approved therapy has been developed to halt the spread of the pathogen, and unfortunately, the strategies for developing a new therapy will require a long time and very extensive resources. Therefore, drug repurposing has emerged as an ideal strategy toward a smart, versatile, quick way to confine the lethal disease. In this endeavor, natural products have been an untapped source for new drugs. This review represents the confederated experience of multidisciplinary researchers of 99 articles using several databases: Google Scholar, Science Direct, MEDLINE, Web of Science, Scopus, and PubMed. To establish the hypothesis, a Bayesian perspective of a systematic review was used to outline evidence synthesis. Our docking documentation of 69 compounds and future research agenda assumptions were directed toward finding an effective and economic anti-COVID-19 treatment from natural products. Glucosinolate, flavones, and sulfated nitrogenous compounds demonstrate direct anti-SARS-CoV-2 activity through inhibition protease enzymes and may be considered potential candidates against coronavirus. These findings could be a starting point to initiate an integrative study that may encompass interested scientists and research institutes to test the hypothesis in vitro, in vivo, and in clinics after satisfying all ethical requirements.

BACKGROUND: Despite reported higher rates and worse outcomes due to COVID-19 in certain racial and ethnic groups, much remains unknown. We explored the association between Hispanic ethnicity and outcomes in COVID-19 patients in Long Island, New York. METHODS: We conducted a retrospective cohort study of 2,039 Hispanic and non-Hispanic Caucasian patients testing positive for SARS-CoV-2 between March 7 and May 23, 2020, at a large suburban academic tertiary care hospital near New York City. We explored the association of ethnicity with need for intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality. RESULTS: Of all patients, 1,079 (53%) were non-Hispanic Caucasians and 960 (47%) were Hispanic. Hispanic patients presented in higher numbers than expected for our catchment area. Compared with Caucasians, Hispanics were younger (45 years vs. 59 years), had fewer comorbidities (66% with no comorbidities vs. 40%), were less likely to have commercial insurance (35% vs. 59%), or were less likely to come from a nursing home (2% vs. 10%). In univariate comparisons, Hispanics were less likely to be admitted (37% vs. 59%) or to die (3% vs. 10%). Age, shortness of breath, congestive heart failure (CHF), coronary artery disease (CAD), hypoxemia, and presentation from nursing homes were associated with admission. Male sex and hypoxemia were associated with ICU admission. Male sex, chronic obstructive pulmonary disease, and hypoxemia were associated with IMV. Male sex, CHF, CAD, and hypoxemia were associated with mortality. After other factors were adjusted for, Hispanics were less likely to be admitted (odds ratio = 0.62, 95% confidence interval = 0.52 to 0.92) but Hispanic ethnicity was not associated with ICU admission, IMV, or mortality. CONCLUSIONS: Hispanics presented at higher rates than average for our population but outcomes among Hispanic patients with COVID-19 were similar to those of Caucasian patients.

Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.

We aimed to summarize reliable medical evidence by the meta-analysis of all published retrospective studies that examined data based on the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by clinical symptoms, molecular (RT-PCR) diagnosis, and characteristic CT imaging features in pregnant women. The MEDLINE, PubMed, Scopus, ISI Web of Science, ClinicalKey, and CINAHL databases were used to select the studies. Then, 384 articles were received, including the studies until 01/May/2020. As a result of the full-text evaluation, 12 retrospective articles covering all the data related were selected. A total of 181 pregnant cases with SARS-CoV-2 infections were included in the meta-analysis within the scope of these articles. According to the results, the incidence of fever was 38.1% (95% CI: 14.2-65%) and cough was 22% (95% CI: 10.8-35.2%) among all clinical features of pregnant cases with SARS-CoV-2 infection. So, fever and cough are the most common symptoms in pregnant cases with SARS-CoV-2 infection, and 91.8% (95% CI: 76.7-99.9%) of RT-PCR results are positive. Moreover, abnormal CT incidence is 97.9% (95% CI: 94.2-99.9%) positive. No case was death. However, as this virus spreads globally, it should not be overlooked that the incidence will increase in pregnant women and maybe in the risky group. RT-PCR and CT can be used together in an accurate and safe diagnosis. In conclusion, these findings will provide important guidance for current studies regarding the clinical features and correct detection of SARS-CoV-2 infection in pregnant women, as well as whether it will create emergency tables that will require the use of a viral drug.

Hospitals worldwide are experiencing a shortage in essential intravenous sedative medications. This is attributable to high number and high sedative needs of COVID-19 critical care patients with disruption of drug supply chains. Inhaled volatile anesthetic agents are an abundant resource and readily implementable solution for providing ICU sedation. Inhaled volatile agents may also provide important pulmonary benefits for COVID-19 patients with ARDS that could improve gas exchange and reduce time spent on a ventilator. We review the use of volatile agents, and provide a technical overview and algorithm for administering inhaled volatile-based sedation in ICUs.

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia tends to affect cardiovascular system and cause cardiovascular damage. This study aimed to explore the prevalence of myocardial injury and risk factors for mortality in patients with COVID-19 pneumonia. METHOD: Two hundred and twenty-four consecutive patients with confirmed diagnosis of SARS-CoV-2 infection and definite outcomes (discharge or death) were retrospectively analyzed. Laboratory results including myocardial biomarkers, oxygen saturation, inflammatory indicators and coagulation function were compared between survivors and non-survivors. Univariate and multivariate logistic regression model were used to explore risk factors for in-hospital mortality, and a chart with different combinations of risk factors was constructed to predict mortality. RESULTS: Two hundred and three patients were included in the final analysis, consisting of 145 patients who recovered and 58 patients who died. Compared with survivors, non-survivors were older, with more comorbidities, more severe inflammation and active coagulation function, higher levels of myocardial biomarkers and lower SaO2. 28 (50%) non-survivors and 9 (6%) survivors developed myocardial injury, which was associated with disease severity at admission. Elevated d-dimer (OR=9.51, 95% CI [3.61-25.0], P<0.001), creatinine kinase-myocardial band (OR=6.93, 95% CI [1.83-26.2], P=0.004), Troponin I (OR=10.1, 95% CI [3.1-32.8], P<0.001) and C-reactive protein (OR=15.1, 95% CI [1.7-129.3], P=0.013) were risk factors for mortality. Patients with abnormal levels of d-dimer, Troponin I and CRP were predicted to have significantly higher probability of death. CONCLUSIONS: Our results suggest that SARS-CoV-2 infection may induce myocardial injury and consequently exacerbate the clinical course and worsen prognosis. Abnormal d-dimer, CK-MB, Troponin I and CRP are risk factors for short-term mortality.

In response to the 2008 economic and financial crisis and to its effects on healthcare systems, dental care has become unaffordable for many people, and a huge number of patients worldwide are avoiding or skipping necessary dental treatments [...].

BACKGROUND: Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19. METHODS: Six different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles related to COVID-19 and neurological complications in children. Studies/case series reporting neurological manifestations of COVID-19 in patients aged

Reports suggest that children aged >/=10 years can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). However, limited data are available on SARS-CoV-2 transmission from young children, particularly in child care settings (3). To better understand transmission from young children, contact tracing data collected from three COVID-19 outbreaks in child care facilities in Salt Lake County, Utah, during April 1-July 10, 2020, were retrospectively reviewed to explore attack rates and transmission patterns. A total of 184 persons, including 110 (60%) children had a known epidemiologic link to one of these three facilities. Among these persons, 31 confirmed COVID-19 cases occurred; 13 (42%) in children. Among pediatric patients with facility-associated confirmed COVID-19, all had mild or no symptoms. Twelve children acquired COVID-19 in child care facilities. Transmission was documented from these children to at least 12 (26%) of 46 nonfacility contacts (confirmed or probable cases). One parent was hospitalized. Transmission was observed from two of three children with confirmed, asymptomatic COVID-19. Detailed contact tracing data show that children can play a role in transmission from child care settings to household contacts. Having SARS-CoV-2 testing available, timely results, and testing of contacts of persons with COVID-19 in child care settings regardless of symptoms can help prevent transmission. CDC guidance for child care programs recommends the use of face masks, particularly among staff members, especially when children are too young to wear masks, along with hand hygiene, frequent cleaning and disinfecting of high-touch surfaces, and staying home when ill to reduce SARS-CoV-2 transmission (4).

Background: Part of the role of the media is to report any issue affecting the society to the masses. Coronavirus has become an issue of transnational concern. The importance of the media in the coverage of coronavirus disease 2019 (COVID-19) in Nigeria and its implications among Nigerian populace cannot be overestimated. This study evaluates how Nigerian media depict the coronavirus pandemic and how the depictions shape people's perception and response to the pandemic. Methods: The study employed a quantitative design (newspaper content analysis and questionnaire). The content analysis examines the nature of media coverage of coronavirus in Nigeria and China using four major national newspapers (The Sun, The Vanguard, The Guardian and The Punch). The period of study ranged from January 2020 to March 2020. A total of 1070newspaper items on coronavirus outbreak were identified across the four newspapers and content-analysed. Results: The finding shows that the coverage of the pandemic was dominated by straight news reports accounting for 763 or (71.3%) of all analysed items. This was followed by opinions 169(15.8%), features 120 (11.2%) and editorials 18 (1.7%) respectively. The Punch 309 (28.9%)reported the outbreak more frequently than The Sun 266 (24.9%), The Guardian 258 (24.1%), and Vanguard 237 (22.1%). Finding further suggests that the framing pattern adopted by the newspapers helped Nigerians to take precautionary measures. Conclusion: Continuous reportage of COVID-19 has proved effective in creating awareness about safety and preventive measures thereby helping to 'flatten the curve' and contain the spread of the virus. However, the newspapers should avoid creating fear/panic in reporting the pandemic.

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0 degrees C, 37.3 degrees C (P = .043), and 37.0 degrees C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.

BACKGROUND: Bromhexine hydrochloride tablets may be effective in the treatment of Coronavirus disease 2019 (COVID-19) in children. This study will further evaluate the efficacy and safety of bromhexine hydrochloride tablets in the treatment of COVID-19 in children. METHODS: The following electronic databases will be searched, with all relevant randomized controlled trials (RCTs) up to August 2020 to be included: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), the Chongqing VIP China Science and Technology Database (VIP), Wanfang, the Technology Periodical Database, and the Chinese Biomedical Literature Database (CBM). As well as the above, Baidu, the International Clinical Trials Registry Platform (ICTRP), Google Scholar, and the Chinese Clinical Trial Registry (ChiCTR) will also be searched to obtain more comprehensive data. Besides, the references of the included literature will also be traced to supplement our search results and to obtain all relevant literature. RESULTS: This systematic review will evaluate the current status of bromhexine hydrochloride in the treatment of COVID-19 in children, to evaluate its efficacy and safety. CONCLUSION: This study will provide the latest evidence for evaluating the efficacy and safety of bromhexine hydrochloride in the treatment of COVID-19 in children. PROSPERO REGISTRATION NUMBER: CRD42020199805. ETHICS AND DISSEMINATION: The private information of individuals will not be published. This systematic review will also not involve endangering participant rights. Ethical approval is not available. The results may be published in peer-reviewed journals or disseminated at relevant conferences.

INTRODUCTION: The novel coronavirus (COVID-19) is a global pandemic. Although the main clinical manifestation of COVID-19 is respiratory involvement, there is evidence suggesting the neuroinvasive potential of COVID-19. There are limited reports of neurological complications of COVID-19 infection in the literature. Herein, we aim to describe 2 members of a family affected by COVID-19, presenting with ascending paresthesia with the final diagnosis of Guillain-Barre syndrome. CASE REPORT: A 38-year-old man presented with a history of ascending paresthesia and bilateral facial droop since 5 days before admission. The medical history was positive for flu-like symptoms affecting all the members of his family. The neurological examination was notable for bilateral peripheral facial paralysis, generalized areflexia, and derceased sensation in distal limbs. The cerebrospinal fluid analysis revealed an albuminocytologic dissociation. In addition, the electromyography-nerve conduction study findings were suggestive of acute axonal-demyelinating polyneuropathy. Meanwhile the patient was treated with a diagnosis of Guillain-Barre syndrome, his 14-year-old daughter presented with a history of progressive paresthesia and weakness. Similar to her father, the paraclinical evaluations were consistent with Guillain-Barre syndrome. Taking into account clinical findings and the outbreak of COVID-19, the suspicion of COVID-19 was proposed. Eventually, on the basis of throat swab samples stand on polymerase chain reaction, the patients were diagnosed with COVID-19. CONCLUSION: Our cases revealed the familial occurrence of Guillain-Barre syndrome after COVID-19 infection. The authors emphasize neurological complications of COVID-19.

COVID-19 has generated a global need for technologies that enable communication, collaboration, education and scientific discourse whilst maintaining physical distance. University closures due to COVID-19 and physical distancing measures disrupt academic activities that previously occurred face-to-face. Restrictions placed on universities due to COVID-19 have precluded most conventional forms of education, assessment, research and scientific discourse. Anatomists now require valid, robust and easy-to-use communication tools to facilitate remote teaching, learning and research. Recent advances in communication, video conferencing and digital technologies may facilitate continuity of teaching and research activities. Examples include highly-interactive video conferencing technology, collaborative tools, social media and networking platforms. In this narrative review, we examine the utility of these technologies in supporting effective communication and professional activities of anatomists during COVID-19 and after.

Though recent reports link SARS-CoV-2 infections with hyper-inflammatory states in children, most children experience no/mild symptoms, and hospitalization and mortality rates are low in the age group. As symptoms are usually mild and seroconversion occurs at low frequencies, it remains unclear whether children significantly contribute to community transmission. Several hypotheses try to explain age-related differences in disease presentation and severity. Possible reasons for milder presentations in children as compared to adults include frequent contact to seasonal coronaviruses, presence of cross-reactive antibodies, and/or co-clearance with other viruses. Increased expression of ACE2 in young people may facilitate virus infection, while limiting inflammation and reducing the risk of severe disease. Further potential factors include recent vaccinations and a more diverse memory T cell repertoire. This manuscript reviews age-related host factors that may protect children from COVID-19 and complications associated, and addresses the confusion around seropositivity and immunity.

The coronavirus (COVID-19) epidemic reported for the first time in Wuhan, China at the end of 2019, which has caused 4648 deaths in China as of July 10, 2020. This study explored the temporal correlation between the case fatality rate (CFR) of COVID-19 and particulate matter (PM) in Wuhan. We conducted a time series analysis to examine the temporal day-by-day associations. We observed a higher CFR of COVID-19 with increasing concentrations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 mum or less (PM10) and fine PM with an aerodynamic diameter of 2.5 mum or less (PM2.5) in the temporal scale. This association may affect patients with mild to severe disease progression and affect their prognosis.

Corona virus disease 2019 (COVID-19) is triggered by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2) and has rapidly developed into a worldwide pandemic. Unlike other SARS viruses, SARS-CoV2 does not solely impact the respiratory system, but additionally leads to inflammation of endothelial cells, microvascular injuries and coagulopathies, thereby affecting multiple organs. Recent reports of patients who were infected with SARS-CoV2 suggest persistent health problems even months after the initial infection. The French maritime pine bark extract Pycnogenol() has demonstrated anti-inflammatory, vascular and endothelium-protective effects in over 90 human clinical studies. It is proposed that Pycnogenol() may be beneficial in supporting recovery and mitigating symptoms and long-term consequences resulting from a SARS-CoV2 infection in COVID-19 patients.

Given the scope and speed of the spread, the COVID-19 pandemic is not only complex but dangerous. Complicated objective factors such as the long-term existence of source of infection, difficulty in completely blocking the transmission route and a large susceptible population suggested that the COVID-19 pandemic might stay with us for long term. Therefore, we should be ready for a tough and long-term battle against the COVID-19 epidemic. The strategy should adhere to the principle of combining emergency response with regular prevention and control measures, and all efforts should be well harnessed in a coordinated way to keep the epidemic under control.

Patients with COVID-19 infection are at risk of acute respiratory disease syndrome (ARDS) and death. The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. Angiotensin receptor blockers and statins upregulate ACE2. Clinical trials are needed to determine whether this drug combination might be used to treat patients with severe COVID-19 infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health emergency, in which its effective treatment and prevention remain obscured. Hyperpyrexia is an elevation of body temperature above 106.7 degrees F (41.5 degrees C) due to an abnormally increased hypothalamic-thermoregulatory set. The pathophysiology, impact, and outcomes of hyperpyrexia in patients with COVID-19 have not yet been studied. Herein, we present clinical features and outcomes of six patients with COVID-19 who had developed hyperpyrexia during hospitalization. All patients expired shortly after the onset of hyperpyrexia. Hyperpyrexia seems to adversely impact the outcomes and mortality in patients with COVID-19. The underlying mechanisms of developing hyperpyrexia in COVID-19 are mysterious. We propose it may be caused by SARS-CoV-2-related brain injury, exuberant immune response, and thrombus formation. More research is needed to verify our results. Understanding the association between hyperpyrexia and SARS-CoV-2 will help to elucidate the COVID-19 pathogenesis, which is mandatory for developing effective treatment strategies.

INTRODUCTION: COVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. MATERIALS AND METHODS: Our study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. RESULTS: Mean age of 554 subjects were 66.21+/-15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2+/-33.6U/L), ALT (34.01+/-49.34U/L), ALP (78.8+/-46.86U/L), GGT (46.25+/-60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT-AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). CONCLUSIONS: ALT-AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.

Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the search for effective treatment and vaccines has been exponentially on the rise. Finding effective treatment has been the core of attention of many scientific reports and antivirals are in the center of those treatments. Numerous antivirals are being studied for the management of the coronavirus disease 2019 (COVID-19) pneumonia caused by the SARS-CoV-2. Remdesivir was the first drug to gain emergency FDA approval to be used in COVID-19. Similarly, favipiravir, an anti-influenza drug, is being studied as a potential agent against COVID-19. Contrastingly, hydroxychloroquine has been a controversial drug in the management of COVID-19. Nevertheless, the National Institute of Health (NIH), along with the World Health Organization (WHO), have discontinued clinical trials for hydroxychloroquine as the drug showed little or no survival benefit. Ivermectin, an antihelminthic drug, has shown antiviral properties previously. Additionally, it was described to be effective in vivo against the SARS-CoV-2. However, its survival benefit in patients with COVID-19 has not been documented. We herein propose the theory of inhaled ivermectin which can attain the desired lung concentration that will render it effective against SARS-CoV-2.

OBJECTIVE: To explore ABO blood group distribution and clinical characteristics in patients with COVID-19. METHODS: The clinical data of 187 patients with COVID-19 seen between January 20, 2020 and March 5, 2020 at the First Hospital of Changsha were retrospectively analyzed. The differences in the ABO blood group distribution between COVID-19 patients and the control group (1991 cases) were analyzed. The relationship between blood type and clinical characteristics was analyzed. RESULTS: Of the 187 patients with COVID-19, 69 had type A (36.90%), 63 had type B (33.69%), 41 had type O (21.92%), and 14 had type AB blood (7.49%). The proportion of patients with type A blood in the COVID-19 group was significantly higher than that in the control group (36.90% vs. 27.47%, P = 0.006), while the proportion of patients with type O blood in the COVID-19 group was significantly lower than that in the control group (21.92% vs. 30.19%, P = 0.018). The risk of COVID-19 was higher for individuals with blood group A than for those with blood group O (OR = 1.849, 95% CI = 1.228-2.768, P = 0.003). The risk of COVID-19 was higher for patients with blood group A than for those with a blood group other than A (OR = 1.544, 95% CI = 1.122-2.104, P = 0.006). Patients with blood group O had a lower risk of COVID-19 than non-O blood group patients (OR = 0.649, 95% CI = 0.457-0.927, P = 0.018). The ABO blood group distribution was related to COVID-19 status. CONCLUSIONS: Patients with blood group A had an increased risk for infection with SARS-CoV-2, whereas blood group O was associated with a decreased risk, indicating that certain ABO blood groups were correlated with SARS-CoV-2 susceptibility. Blood type was related to some clinical characteristics of patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n = 84) and nondiabetes (n = 500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared with nondiabetic patients, diabetic patients had higher levels of neutrophils (P = .014), C-reactive protein (P = .008), procalcitonin (P < .01), and D-dimer (P = .033), and lower levels of lymphocytes (P = .032) and albumin (P = .035). Furthermore, diabetic patients had a significantly higher incidence of bilateral pneumonia (86.9%, P = .020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs 24.2%, P = .022), acute cardiac injury (47.4% vs 21.2%, P < .01), and death (20.2% vs 8.0%, P = .001) in the diabetes group was significantly higher than that in the nondiabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (hazard ratio 2.180, P = .031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin-required and non-insulin-required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2. CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.

Since December 2019, the infection of the new coronavirus (COVID-19) caused an outbreak of new coronavirus pneumonia in Wuhan, China, and caused great public concern. Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. In addition, ACE2 is a potential therapeutic target. This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.

Coronavirus Disease-2019 (COVID-19) is currently a public health emergency and has been listed by the World Health Organization (WHO) as a pandemic. It has commonly been associated with pulmonary manifestations and there is a growing body of evidence of multisystem involvement of the virus. As evidenced by various case reports and cohort studies, COVID-19-associated coagulopathy has been a common manifestation amongst the critically ill and has been associated with increased mortality. The presence of venous thromboembolic events in patients who are critically ill due to COVID-19 has prompted the adoption of anticoagulation regimens aimed at preventing thromboembolic phenomena. Coagulation abnormalities have also been implicated in the progression and the severity of COVID-19 related acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). There is strong evidence that D-dimer levels help predict which patients are at risk of thromboembolic events, progression to ARDS, DIC, immune dysregulation and mortality. We will review the utility of D-dimer as screening tool and in the risk stratification of COVID-19 patients prone to developing thromboembolic events, DIC, immune dysregulation and death. To date, the studies that have been published show the presence of elevated D-dimer levels in both the adult and pediatric populations and the measured level correlates with disease severity. Studies have also shown the relative increase of D-dimer levels in non-survivors compared to survivors. The elevation of D-dimer levels has shown to guide clinical decision making, namely the initiation of therapeutic anticoagulation and mortality benefit in patients with severe COVID-19 pneumonia compared to severe non COVID-19 pneumonia. Although the current body of literature suggested the use of D-dimer as a risk stratification tool and as a test to augment clinical judgement regarding the initiation of anticoagulation, randomized control trials are needed to fully understand the relationship between COVID-19 infection and the efficacy of D-dimer assays in clinical decision making.

BACKGROUND: Little is known on the trends of aeromedical retrieval (AR) during social isolation. AIM: To compare the pre, lockdown, and post-lockdown AR patient characteristics during a period of Coronavirus 2019 (COVID-19) social isolation. METHODS: An observational study with retrospective data collection, consisting of AR between 26 January and 23 June 2020. RESULTS: There were 16 981 AR consisting of 1983 (11.7%) primary evacuations and 14 998 (88.3%) inter-hospital transfers, with a population median age of 52 years (interquartile range 29.0-69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were six confirmed and 230 suspected cases of COVID-19, with the majority of cases (n = 134; 58.3%) in the social isolation period. As compared to pre-restriction, the odds of retrieval for the restriction and post-restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post-restriction periods (odds ratio (OR) 1.12, 95% confidence interval (CI) 1.02-1.24 and OR 1.18 95%, CI 1.08-1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31, 95% CI 1.04-1.64) and increases for congenital conditions in the restriction period (OR 2.56, 95% CI 1.39-4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72, 95% CI 0.53-0.98). There were lower odds during the post-restriction period for retrievals of the respiratory system (OR 0.78, 95% CI 0.67-0.93), and disease of the skin (OR 0.78, 95% CI 0.6-1.0). Distribution between the 2019 and 2020 time periods differed (P < 0.05), with the lockdown period resulting in a significant reduction in activity. CONCLUSION: The lockdown period resulted in increased AR rates of circulatory and congenital conditions.

Since the outbreak of 2019 novel coronavirus (SARS-CoV-2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID-19) among these patients with preexisting ILD. We analyzed the incidence and severity of COVID-19 patients with ILD among 3201 COVID-19 inpatients, and compared two independent cohorts of COVID-19 patients with pre-existing ILD (n = 28) and non-ILD COVID-19 patients (n = 130). Among those 3201 COVID-19 inpatients, 28 of whom were COVID-19 with ILD (0.88%). Fever was the predominant symptom both in COVID-19 with ILD (81.54%) and non-ILD COVID-19 patients (72.22%). However, COVID-19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. A very significantly higher number of neutrophils, monocytes, interleukin (IL)-8, IL-10, IL-1beta, and D-Dimer was characterized in COVID-19 with ILD as compared to those of non-ILD COVID-19 patients. Furthermore, logistic regression models showed neutrophils counts, proinflammatory cytokines (tumor necrosis factor-alpha, IL6, IL1beta, IL2R), and coagulation dysfunction biomarkers (D-Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID-19. ILD patients could be less vulnerable to SARS-CoV-2. However, ILD patients tend to severity condition after being infected with SARS-CoV-2. The prognosis of COVID-19 patients with per-existing ILD is significantly worse than that of non-ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID-19 patients with ILD.

The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson's coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson's coefficients between -0.47 and -0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1-35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1-41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.

PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.

BACKGROUND: The population in Mexico has high prevalence rates of noncommunicable diseases (NCDs). Hospitalization and death of COVID-19 patients in the countries most affected by the pandemic has been associated to chronic comorbidities. OBJECTIVE: To describe the prevalence of NCDs in patients with COVID-19 in Mexico and analyze the increased risk due to comorbidities and risk factors on hospitalization, utilization of intensive care units and death. METHODS: A cross-sectional study was performed from 212,802 confirmed COVID-19 cases reported by the Ministry of Health up to June 27, 2020. Odds ratios were performed using logistic regression model. RESULTS: Up to 47.40% of patients with COVID-19 diagnosis were also reported with a comorbidity, with hypertension being the most frequent (20.12%). The report of at least one NCD significantly increased the risk of death with respect to patients without such diagnoses. Chronic kidney disease increased the risk of death the most (OR 2.31), followed by diabetes (OR 1.69), immunosuppression (OR 1.62), obesity (OR 1.42), hypertension (OR 1.24), chronic obstructive pulmonary disease (OR 1.20). The comorbidities that most increased the risk of ICU and of intubation were diabetes, immunosuppression and obesity. CONCLUSION: NCD comorbidities increase the severity of COVID-19 infection. Given high NCD prevalence rates among the Mexican population, the pandemic poses a special threat to the health system and to society. Special prevention measures need to be strengthened for persons with NCD diagnoses in the short-term. In the mid-term, disease control strategies need to be improved to protect these patients against COVID-19 severity.

We present a phylodynamic and phylogeographic analysis of this new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in this report. A tree of maximum credibility was constructed using the 72 entire genome sequences of this virus, from the three countries (China, Italy, and Spain) available as of 26 March 2020 on the GISAID reference frame. To schematize the current SARS-CoV-2 migration scenario between and within the three countries chosen, using the multitype bearth-death model implemented in BEAST2. Bayesian phylogeographic reconstruction shows that SARS-CoV-2 has a rate of evolution of 2.11 x 10(-3) per sites per year (95% highest posterior density: 1.56 x 10(-3) to 3.89 x 10(-3) ), and a geographic origin in Shanghai, where time until the most recent common ancestor (tMRCA) emerged, according to the analysis of the molecular clock, around 13 November 2019. While for Italy and Spain, there are two tMRCA for each country, which agree with the assumption of several introductions for these countries. That explains also this very short period of subepidermal circulation before the recent events. A total of 8 (median) migration events occurred during this short period, the largest proportion of which (6 events [75%]) occurred from Shanghai (China) to Spain and from Italy to Spain. Such events are marked by speeds of migration that are comparatively lower as compared with that from Shanghai to Italy. Shanghai's R0 and Italy's are closer to each other, though Spain's is slightly higher. All these results allow us to conclude the need for an automatic system of mixed, molecular and classical epidemiological surveillance, which could play a role in this global surveillance of public health and decision-making.

BACKGROUND: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. OBJECTIVE: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). METHODS: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. RESULTS: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and TH17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. CONCLUSION: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.